Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate. 相似文献
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study.
Methods
In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96.
Results
Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0–98.1) and 74.4% (64/86; 95% CI 63.9–83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR −2.3, 2.0). Median self-reported adherence was 100% (IQR 100–100%).
Conclusions
Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population. 相似文献
Background and AimsThe therapeutic effect of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir (ETV) on chronic hepatitis B (CHB) patients remains inconsistent. The aim of this study was to explore the differences in virological responses to TAF, TDF and ETV in patients with CHB.MethodsLiterature searches were conducted of the PubMed, EMBASE, and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21, 2020. Statistical comparisons of virological response between TDF, ETV, and TAF were carried out with pooled odds ratio (OR) values.ResultsThe virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks [OR=1.12, 95% confidence interval (CI): 0.89–1.41], 24-weeks (OR=1.33, 95% CI: 1.11–1.61), 48-weeks (OR=1.62, 95% CI: 1.16–2.25), 72-weeks (OR=1.43, 95% CI: 0.78–2.62), and 96-weeks (OR=1.56, 95% CI: 0.87–2.81) treatment. No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF. The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks, 48-weeks (OR=1.54, 95% CI: 1.17–2.02), 96-weeks, and 144-weeks.ConclusionsThe virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients, but there was no significant difference between TAF and TDF. In addition, the therapeutic effect of TDF+ETV was superior to TDF alone. 相似文献
Evaluate the impact of switching to an anti-retroviral regimen containing tenofovir alafenamide (TAF) on weight and the development of metabolic complications compared to remaining on a non-TAF containing regimen.Single-center retrospective case-control study.We evaluated people living with human immunodeficiency virus (PLWH) who were on an anti-retroviral regimen not containing TAF and were switched to a regimen containing TAF between January 1, 2016 and September 30, 2018. The control group included PLWH on a TAF free regimen throughout the study period. The primary outcome was change in weight from baseline to 12 months postswitch. Secondary outcomes included percent change in weight, change in body mass index (BMI), change in BMI class, and new diagnoses of diabetes, hypertension, and hyperlipidemia (HLD) during the study period.PLWH switched to TAF (n = 446) demonstrated significantly greater mean increase in weight compared to the control group (n = 162) (1.97 vs 0.88 kg, P = .01), however the effect was only seen in those switched from tenofovir disoproxil fumarate. Those that switched to TAF also had a significantly higher percent increase in weight, increase in BMI, and BMI class. We observed a higher rate of new diagnosis of HLD in the control group compared to the TAF switch group during the study period.PLWH switched to TAF had greater increases in weight after 1 year as compared to those continuing on a TAF free regimen. However, this did not translate to higher rates of obesity related illnesses such as diabetes, hypertension, and HLD during the follow up period. 相似文献
Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown.
Methods
Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models.
Results
Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36–.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91–2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17–2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62–.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56–.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07–.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022.
Conclusions
The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort. 相似文献
Tenofovir disoproxil fumarate (TDF) is active against hepatitis B virus (HBV) and HIV. However, the long‐term efficacy of tenofovir disoproxil fumarate (TDF) is not well known and the appearance of resistance is a major concern. We have studied the efficacy of TDF against HBV in patients treated at an Infectious Diseases Unit.
Methods
We carried out a retrospective observational study of the efficacy of TDF against HBV replication in a cohort of 52 HIV‐coinfected patients who received TDF for at least 6 months.
Results
The median duration of follow‐up of TDF treatment was 34 months. Forty‐one patients (79%) were positive for HBV envelope antigen (HBeAg) and 35 had received previous lamivudine monotherapy for a median duration of 32 months. Virological breakthrough was observed in nine cases (17%). At the end of the follow‐up period, HBV DNA levels were <1000 copies/mL in 42 patients (81%) and <200 copies/mL in 31 patients (60%). There were no significant differences between the lamivudine‐naïve and lamivudine‐experienced groups. In the lamivudine‐experienced group, the duration of previous lamivudine monotherapy was associated with failure to achieve HBV DNA levels <200 copies/mL (P=0.036). Adding lamivudine or emtricitabine to TDF did not improve virological suppression. In 39 patients who achieved <200 HBV DNA copies/mL during TDF treatment, virological breakthrough was seen only in two patients (5%) after a median follow‐up duration of 39.7 months.
Conclusions
TDF was able to control HBV replication in most HIV‐coinfected patients after a median follow‐up duration of 34 months, regardless of previous lamivudine treatment. However, a sizeable proportion of patients developed virological breakthrough. 相似文献
HIV is associated with chronic obstructive pulmonary disease (COPD) in high resource settings. Similar relationships are less understood in low resource settings. We aimed to estimate the association between HIV infection, tuberculosis, and COPD in rural Uganda.
Methods
The Uganda Non-communicable Diseases and Aging Cohort study observes people 40 years and older living with HIV (PLWH) on antiretroviral therapy, and population-based HIV-uninfected controls in rural Uganda. Participants completed respiratory questionnaires and post-bronchodilator spirometry.
Results
Among 269 participants with spirometry, median age was 52 (IQR 48–55), 48% (n?=?130) were ever-smokers, and few (3%, n?=?9) reported a history of COPD or asthma. All participants with prior tuberculosis (7%, n?=?18) were PLWH. Among 143 (53%) PLWH, median CD4 count was 477?cells/mm3 and 131 (92%) were virologically suppressed. FEV1 was lower among older individuals (??0.5%pred/year, 95% CI 0.2–0.8, p?<?0.01) and those with a history of tuberculosis (??14.4%pred, 95% CI ??23.5 to ??5.3, p?<?0.01). COPD was diagnosed in 9 (4%) participants, eight of whom (89%) were PLWH, six of whom (67%) had a history of tuberculosis, and all of whom (100%) were men. Among 287 participants with complete symptom questionnaires, respiratory symptoms were more likely among women (AOR 3.9, 95% CI 2.0–7.7, p?<?0.001) and those in homes cooking with charcoal (AOR 3.2, 95% CI 1.4–7.4, p?=?0.008).
Conclusion
In rural Uganda, COPD may be more prevalent among PLWH, men, and those with prior tuberculosis. Future research is needed to confirm these findings and evaluate their broader impacts on health.
An open‐label, three‐period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF).
Methods
Thirty‐six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty‐four‐hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady‐state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals.
Results
After TDF coadministration, APV geometric mean minimum concentration (Cmin), maximum concentration (Cmax), and area under the plasma concentration–time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV Cmin, Cmax and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods.
Conclusions
In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant. 相似文献
Background/AimsThe incidence and relapse pattern in patients stopping tenofovir alafenamide (TAF), a prodrug of tenofovir which is more concentrated in hepatocytes, is unknown.MethodsHBeAg-negative CHB patients stopping tenofovir disoproxil fumarate (TDF) (off-TDF) or who had switched to TAF more than 3 months before discontinuation (off-TAF) were recruited. The propensity score-matching method (PSM) was used, creating a ratio of 1:3 between the off-TAF versus the off-TDF groups to adjust for associated factors.ResultsAfter PSM, 180 off-TDF and 60 off-TAF patients were analyzed. The cumulative rates of virological and clinical relapse at 52 weeks were 75.1% and 58.5% respectively in the off-TDF group and 91.1% and 61.6% in the off-TAF group. Patients in the off-TAF group had significantly higher rates of virological relapse than those in the off-TDF group (p = 0.021), but not clinical relapse (p = 0.785). Multivariate cox regression analysis showed that off-TAF group was an independent factor for virological relapse, but not clinical relapse. Severity of clinical relapse and hepatic decompensation rate were comparable between off-TDF and off-TAF groupsConclusionsThe off-TAF group had a higher virological relapse rate than the off-TDF group. The difference in clinical relapse pattern and severity was not clinically important between the two groups. 相似文献
Pulmonary hypertension is a life-limiting complication of interstitial lung disease (ILD-PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD-PH was associated with improved survival.
Methods
Consecutive incident patients with ILD-PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow-up and survival data modelled by Bayesian methods.
Results
The diagnoses in 128 patients were idiopathic pulmonary fibrosis (n = 74, 58%), hypersensitivity pneumonitis (n = 17, 13%), non-specific interstitial pneumonia (n = 12, 9%), undifferentiated ILD (n = 8, 6%) and other lung diseases (n = 17, 13%). Final outcomes were death (n = 106, 83%), transplantation (n = 9, 7%) and censoring (n = 13, 10%). Patients treated with PDE5i (n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC; median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p=0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint-modelling (HR 0.39, 95% CI: 0.23, 0.59, p < 0.001) and propensity-matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p < 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: −0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04).
Conclusion
PDE5i treatment in ILD-PH should be investigated by a prospective randomized trial. 相似文献
The combination of didanosine (ddI) and tenofovir (TDF) has potential advantages, but because of several pitfalls (unexpected decreases in CD4+ T cells, increased risk of pancreatitis) its use has been questioned. Since anecdotal cases of transient insulin-dependent diabetes mellitus were seen in our clinic in patients on ddI + TDF-containing regimens, we explored the rate of this complication in more detail. Retrospective analysis of plasma glucose levels in patients who completed 12 months of treatment with three different triple antiretroviral regimens including ddI + TDF, TDF, or ddI was done. Patients taking antidiabetic drugs and/or those with baseline glucose levels >125 mg/dl were excluded. Weight, age, concomitant antiretrovirals, and ddI dose were assessed. At 12 months without treatment changes, fasting glucose levels were compared to baseline. A multivariate analysis was performed to evaluate which variables were associated with glucose elevations. A total of 177 HIV-infected patients were assessed (78 on ddI + TDF, 42 on TDF, and 57 on ddI). Mean baseline features were well balanced between groups for age (mean, 39 years), gender (78% male), CD4+ count (mean, 507 cells/mm3), weight (mean, 67 kg), and glucose level (mean, 95 mg/dl). There were only significant differences between groups for baseline viral load and protease inhibitor (PI) use (13% in the ddI + TDF arm vs. 7% and 9% in the TDF and ddI arms, respectively). At 12 months, 60% of the patients in the ddI + TDF arm were taking ddI 250 mg/day and the rest were on ddI 400 mg/day. At 12 months, hyperglycemia was significantly more frequent in the ddI + TDF arm (33%) when compared to patients on TDF or ddI separately (5% and 10%, respectively). In the multiple linear regression analysis, a lower weight (beta -0.35; 95% CI -0.67 to -0.03; p = 0.033) and use of ddI + TDF (beta: 13.05; 95% CI: 0.2 to 26; p = 0.047) were independently associated with a higher risk of developing hyperglycemia. The risk of hyperglycemia is increased in patients treated with ddI + TDF, particularly in those with lower weight. As high ddI exposure has been associated with endocrine pancreatic dysfunction and diabetes, ddI "overdosing" as result of concomitant TDF use and low weight might explain our findings. These results add a further note of caution to the use of TDF and ddI in combination. 相似文献
The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)‐naïve Japanese chronic hepatitis B (CHB) patients.
Methods
This multicenter, randomized, double‐blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA‐naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non‐inferiority of TDF to ETV at week 24.
Results
A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)‐DNA levels from baseline to week 24 was ?4.63 ± 0.044 and ?4.50 ± 0.063 log10 copies/mL in the TDF and ETV arms, respectively, indicating the non‐inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV‐DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis B surface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug‐related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively.
Conclusions
The study is the first to report that TDF has non‐inferiority to ETV in treatment effectiveness (lowering of serum HBV‐DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409. 相似文献
The incidence and predictors of 30-day stroke after transcatheter aortic valve replacement (TAVR) were derived from early studies investigating first-generation devices. The incidence of 6-month stroke and its related predictors are unknown.
Aims
To investigate the incidence and to identify procedural and patient-related predictors of 30-day and 6-month stroke after TAVR.
Methods
Data from 2753 consecutive patients with severe aortic stenosis undergoing TAVR were obtained from the OBSERVANT-II study, an observational, prospective, multicenter cohort study. The study endpoints were symptomatic 30-day and 6-month stroke after TAVR.
Results
The occurrence of a 30-day and 6-month stroke was low (1.3% and 2.4%, respectively) but with significant impact on survival. Aortic valve predilatation (odds ratio [OR]: 2.28, 95% confidence interval [CI]: 1.12–4.65, p = 0.023), diabetes (OR: 3.10, 95% CI: 1.56–6.18, p = 0.001), and left ventricle ejection fraction < 50% (OR: 2.15, 95% CI: 1.04–4.47, p = 0.04) were independent predictors of 30-day stroke, whereas diabetes (sub-distribution hazard ratio [SHR]: 2.07, 95% CI: 1.25–3.42, p = 0.004), pre-existing neurological dysfunction (SHR: 3.92, 95% CI: 1.54–10, p = 0.004), bicuspid valve (SHR: 4.75, 95% CI: 1.44–15.7, p = 0.011), and critical status (SHR: 3.05, 95% CI: 1.21–7.72, p = 0.018) were predictive of 6-month stroke. Conversely, antiplatelet therapy and anticoagulation were protective factors at both 30 days and 6 months.
Conclusions
Stroke after TAVR was rare. Predilatation was the only procedural factor predictive of 30-day stroke, whereas the remaining were patient-related risk factors, suggesting appropriate risk stratification preoperatively. 相似文献
The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV‐coinfected individuals receiving tenofovir (TDF).
Methods
This retrospective cross‐sectional study identified 28 HIV/HBV‐coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on‐TDF), and 24 also had samples available prior to treatment (pre‐TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (±3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR‐positive samples was sequenced and compared with reference HBV data.
Results
Of the pre‐TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on‐TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3–23 months). Lamivudine (3TC)‐resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF‐resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.
Conclusions
Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC‐resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF. 相似文献
Our purpose of this study is to evaluate the effect and safety of macitentan in the treatment of pulmonary hypertension (PH).
Methods
We retrieved the safety and efficacy of macitentan treatment for PH using PubMed, the Cochrane Library, EMBASE databases and clinicaltrials.gov . The Cochrane Risk of Bias Tool was used for literature screening and quality assessment. Data analysis was conducted using RevMan 5.4.1 and Stata/SE 15.1 software. Results are presented as standardization mean differences (SMDs) and odds ratio (OR).
Results
Meta-analysis of seven randomized controlled trial (RCT) studies and four non-RCT studies with 2769 patients was included, involving 723 in the macitentan group and 599 in the placebo group. The results of the study showed that macitentan had effectively decreased pulmonary vascular resistance (PVR) (SMD = −0.53, 95% CI: −0.77–−0.29, p < 0.05), cardiac index (CI) (SMD = 0.60, 95% CI: 0.37–0.83, p < 0.05) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = −0.22, 95% CI: −0.40–−0.03, p < 0.05). Furthermore, macitentan also significantly reduced PVR (SMD = −0.58, 95% CI: −0.80–−0.35, p < 0.05), 6-min walk distance (6WMD) (SMD = 0.33, 95% CI: 0.15–0.50, p < 0.05), CI (SMD = 0.48, 95% CI: 0.28–0.69, p < 0.05), mean pulmonary arterial pressure (mPAP) (SMD = −0.43, 95% CI: −0.64–−0.23, p < 0.05) and NT-proBNP (SMD = −0.55, 95% CI: −1.07–−0.03, p < 0.05) between baseline and follow-up. The adverse reactions to macitentan were mild, with headache, anaemia and bronchitis. Other efficacy and safety outcomes did not reach statistical differences.
Conclusion
Macitentan therapy for PH is effective and safe. The effectiveness on PVR, mPAP, mean right atrial pressure (mRAP), mortality and other indicators still needs to be further confirmed. 相似文献
Pancreatic cancer is one of the most lethal cancers worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in tumor immunity. It has been reported that polymorphisms in CD86 gene can be involved in the development of various cancers. Here, we investigated the association of two CD86 polymorphisms, +1057G/A (rs1129055) and +2379G/C (rs17281995), with pancreatic cancer in the Chinese population.
Methods
The two polymorphisms were identified in 369 pancreatic cancer patients and 412 healthy controls using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Data were analyzed by chi-square test and adjusted for body mass index, smoking, drinking, and diabetes status.
Results
Results showed that the frequency of the +1057A allele was significantly higher in pancreatic cancer cases than in controls (59.8 vs. 52.8?%, p?=?0.021). Comparison of genotype frequencies showed that +1057GA and +1057AA genotypes were significantly increased in the pancreatic cancer group (odds ratio (OR)?=?1.52; 95?% confidence interval (CI), 1.09–2.38; p?=?0.026; and OR?=?1.90; 95?% CI, 1.21–3.01; p?=?0.007). We did not find any association between the +2379G/C polymorphism and pancreatic cancer. Analysis of haplotypes indicated that the AG (+1057, +2379) haplotype was correlated with the susceptibility to this disease (p?=?0.019).
Conclusions
These results suggest that the CD86 +1057G/A polymorphism and AG (+1057, +2379) haplotype are genetic risk factors for pancreatic cancer. 相似文献
OBJECTIVE: To compare the safety and efficacy of two once-daily antiretroviral regimens containing lamivudine (3TC) or tenofovir disoproxil fumarate (TDF), each administered with didanosine (ddI) and efavirenz (EFV) as initial therapy to HIV-1-infected subjects. METHODS: Single centre, randomized (1: 1), open-label study in antiretroviral-naive, HIV-infected adults. Subjects commenced either 3TC/ddI/EFV (3TC group) or TDF/ddI/EFV (TDF group). Safety, Medication Event Monitoring System (MEMScap) and plasma EFV concentration monitoring was performed over the study period. Comparisons between groups were assessed using chi test and linear regression analysis was used to assess the relationship between EFV concentrations and virological response. RESULTS: Seventy-seven subjects were enrolled prior to recruitment being suspended, 36 to the 3TC group and 41 to the TDF group. Intention-to-treat analysis in which last observation carried forward (LOCF) found the mean viral log10 load [95% confidence interval (CI)] at weeks 4 and 12 to be 2.67 (2.47-2.87) and 1.83 (1.74-1.92) for the 3TC group and 2.75 (2.45-3.05) and 2.28 (1.96-2.6) for the TDF group (P = 0.013). Emergence of resistance occurred in five of 41 (12.2%) subjects in the TDF group up to week 12 compared with none of 36 in the 3TC group, (P < 0.05); these five subjects shared similar baseline characteristics (CD4+ cell counts < 200 x 10 cells/l and HIV-1 RNA > 100,000 copies/ml). Despite MEMScap monitoring showing > 99% adherence in all subjects, among the five failures, three had low EFV concentrations. CONCLUSION: TDF/ddI/EFV as initial therapy appears to have diminished efficacy in subjects with CD4 < 200 x 10 cells/l and viral load > 100,000 copies/ml. Treatment failure with resistance was not attributable to baseline resistance, efavirenz exposure or poor adherence. 相似文献
ABSTRACTPerson-centred care (PCC) for people living with HIV (PLWH) is a global goal for WHO and the UNAIDS strategy. We aimed to develop a novel person-centred intervention for community providers, test the feasibility of participant recruitment and retention, intervention delivery and to establish acceptability. Findings from qualitative interviews with PLWH and healthcare professionals were mapped onto a PCC theory in an expert intervention development workshop. A parallel feasibility cluster randomised controlled trial (cRCT) was conducted. We randomly assigned clusters (1:1) either to intervention or to standard care. The primary outcome was trial recruitment and retention. We screened 83 PLWH, enrolled 60 with 30 allocated to each arm. Recruitment and retention rates were 87% and 97%, respectively. Potential effect size achieved at final timepoint: a measure of person-centred outcomes [0.7 (95% CI 0.17–1.23) p?<?0.001]; MOSHIV [0.7 (95% CI 0.17–1.23) p?<?0.001]; Patient Experience Questionnaire [0.8 (95% CI 0.27–1.31) p?<?0.001]; CARE Measure [1.0 (95% CI 0.45–1.55) p?<?0.001], POSITIVE OUTCOMES [0.7 (95% CI 0.17–1.23) p?<?0.001]. Post-trial interviews revealed general acceptability of the intervention. The results confirm the feasibility and justify a definitive cRCT of the enhanced care intervention to improve person-centred outcomes for PLWH.Trial registration number ISRCTN13630241. 相似文献
Available data are limited concerning long-term lung function (LF) evolution after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in lung transplant (LT) recipients. The aim of this study is to determine the effect of first SARS-CoV-2 infection on long-term LF in LT recipients. We analyzed spirometry results of LT recipients followed at our institution (March 2020 to July 2022) at 3, 6, and 12 months after first SARS-CoV-2 infection. Overall, 42 LT patients of our cohort (70%) with COVID-19 were included for long-term LF analysis. Forced expiratory volume in 1 s (FEV1) declined significantly at 3 months (−4.5%, −97 mL, 95% CI [−163; −31], p < .01), but not at 6 and 12 months (−3.9%, −65 mL, 95% CI [−168; +39], p = .21). Results were quite similar for the forced vital capacity. Spirometry values declined significantly at 3 months after COVID-19 in LT recipients, presented a mixed decline at 6 months, and no significant decline at 12 months.
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