ABSTRACT
BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection. METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct a personalized estimation of arterial systolic blood pressure, arterial diastolic blood pressure, and oxygen saturation. RESULTS: The proposed method was evaluated with a subset of 1,732 subjects from the publicly available ICU dataset MIMIC III. The mean absolute error is 2.52 ± 2.43 mmHg for systolic blood pressure, 1.37 ± 1.89 mmHg for diastolic blood pressure, and 0.58 ± 0.79% for oxygen saturation, which satisfies the requirements of the Association of Advancement of Medical Instrumentation standard and achieve grades A for the British Hypertension Society standard. CONCLUSIONS: The results indicate that our model meets clinical standards and could potentially boost the accuracy of blood pressure and oxygen saturation measurement to deliver high-quality healthcare.
Subject(s)
Deep Learning , Hypertension , Humans , Arterial Pressure , Blood Pressure/physiology , Photoplethysmography/methods , Arteries , Hypertension/diagnosisABSTRACT
BACKGROUND: For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up. METHODS: In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT)â >2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis. RESULTS: All patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation. CONCLUSION: Among HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur >3 months after end of therapy. CLINICAL TRIALS REGISTRATION: NCT02613871.
Subject(s)
Coinfection , Hepatitis B , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents , Benzimidazoles , DNA, Viral , Fluorenes , Follow-Up Studies , Hepacivirus/genetics , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Hepatitis C/complications , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Sofosbuvir/therapeutic use , TaiwanABSTRACT
BACKGROUND/PURPOSE: The association between herpetic/bacterial co-infection and periodontal diseases has been reported. However, how interactions between herpesviruses and periodontal bacteria dampen periodontal inflammation is still unclear. This study determined effects of co-infection with oral bacteria, including Streptococcus sanguinis, Fusobacterium nucleatum or Aggregatibacter actinomycetemcomitans, in herpes simplex virus type 1 (HSV-1)-infected oral epithelial cells. METHODS: Cell viability was determined by detection the activity of mitochondrial dehydrogenase. Viral production was measured using the plaque assay. Levels of bacterial and viral DNA were determined by real-time polymerase chain reaction. Secretion of interleukin (IL)-6 and IL-8 was measured using the enzyme-linked immunosorbent assay. RESULTS: Viability was not further reduced by bacterial co-infection in HSV-1-infected cells. Co-infection with HSV-1 and S. sanguinis or F. nucleatum reduced the viral yield whereas co-infection with HSV-1 and A. actinomycetemcomitans significantly enhanced the viral yield in oral epithelial cells. The enhancing effect of A. actinomycetemcomitans was not affected by bacterial heat-inactivation. Co-infection with HSV-1/A. actinomycetemcomitans increased intracellular levels of both viral and bacterial DNA. Secretion of IL-6 and IL-8 stimulated by A. actinomycetemcomitans infection was partly reduced by co-infection with HSV-1 in oral epithelial cells. CONCLUSION: In contrast to S. sanguinis and F. nucleatum, A. actinomycetemcomitans enhanced the yield of HSV-1. Either HSV-1 or A. actinomycetemcomitans may be benefited from co-infection, in aspects of increases in production of viral and bacterial DNA as well as reductions in cytokine secretion. These findings echoed with previous clinical studies showing co-infection of HSV and A. actinomycetemcomitans in patients with aggressive periodontitis.
Subject(s)
Aggressive Periodontitis , Coinfection , Herpesvirus 1, Human , Aggregatibacter actinomycetemcomitans , DNA, Bacterial , Epithelial Cells , Humans , Interleukin-6 , Interleukin-8ABSTRACT
BACKGROUND: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, cirrhosis, and liver cancer. Most of the infected people have no clinical symptoms. The current strategy for HCV elimination includes test and treatment. In this study, we aimed to evaluate the campaign for retrieving patients who were lost to follow-up, for subsequent re-evaluation. METHODS: From January 2020 to October 2020, patients who had prior tests for positive anti-HCV antibody in 2010-2018 in our hospital were enrolled for our patient callback campaign. Patients who had unknown HCV RNA status or no documented successful antiviral therapy history were selected for anti-HCV therapy re-evaluation. To facilitate patient referral in the hospital, we developed an electronic reminding system and called the candidate patients via telephone during the study period. RESULTS: Through the hospital electronic system, 3783 patients with positive anti-HCV antibody documentation were identified. Among them, 1446 (38.22%) had tested negative for HCV RNA or had anti-HCV therapy, thereby excluded. Of the 2337 eligible patients, 1472 (62.99%) were successfully contacted and called back during the study period for subsequent HCV RNA testing and therapy. We found that 42.19% of the patients had positive HCV RNA and 88% received subsequent anti-HCV therapy. CONCLUSIONS: A significant number of patients with positive HCV serology were lost for HCV confirmatory test or therapy in the hospital. Therefore, this targeted HCV callback approach in the hospital is feasible and effective in achieving microelimination.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C Antibodies , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/drug therapy , Retrospective StudiesABSTRACT
OBJECTIVES: Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2-dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. METHODS: Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. RESULTS: A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase-to-platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two-dimensional SWE and TE were strongly correlated (r = 0.885-0.897; P < .001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy. CONCLUSIONS: Direct-acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy.
Subject(s)
Elasticity Imaging Techniques , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnostic imaging , Hepatitis C, Chronic/drug therapy , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Middle Aged , Retrospective StudiesABSTRACT
The life cycle of leaves, from sprout to senescence, is the phenomenon of regular changes such as budding, branching, leaf spreading, flowering, fruiting, leaf fall, and dormancy due to seasonal climate changes. It is the effect of temperature and moisture in the life cycle on physiological changes, so the detection of newly grown leaves (NGL) is helpful for the estimation of tree growth and even climate change. This study focused on the detection of NGL based on deep learning convolutional neural network (CNN) models with sparse enhancement (SE). As the NGL areas found in forest images have similar sparse characteristics, we used a sparse image to enhance the signal of the NGL. The difference between the NGL and the background could be further improved. We then proposed hybrid CNN models that combined U-net and SegNet features to perform image segmentation. As the NGL in the image were relatively small and tiny targets, in terms of data characteristics, they also belonged to the problem of imbalanced data. Therefore, this paper further proposed 3-Layer SegNet, 3-Layer U-SegNet, 2-Layer U-SegNet, and 2-Layer Conv-U-SegNet architectures to reduce the pooling degree of traditional semantic segmentation models, and used a loss function to increase the weight of the NGL. According to the experimental results, our proposed algorithms were indeed helpful for the image segmentation of NGL and could achieve better kappa results by 0.743.
Subject(s)
Deep Learning , Image Processing, Computer-Assisted , Neural Networks, Computer , Plant Leaves , TreesABSTRACT
Grain moisture content (GMC) is a key indicator of the appropriate harvest period of rice. Conventional testing is time-consuming and laborious, thus not to be implemented over vast areas and to enable the estimation of future changes for revealing optimal harvesting. Images of single panicles were shot with smartphones and corrected using a spectral-geometric correction board. In total, 86 panicle samples were obtained each time and then dried at 80 °C for 7 days to acquire the wet-basis GMC. In total, 517 valid samples were obtained, in which 80% was randomly used for training and 20% was used for testing to construct the image-based GMC assessment model. In total, 17 GMC surveys from a total of 201 samples were also performed from an area of 1 m2 representing on-site GMC, which enabled a multi-day GMC prediction. Eight color indices were selected using principal component analysis for building four machine learning models, including random forest, multilayer perceptron, support vector regression (SVR), and multivariate linear regression. The SVR model with a MAE of 1.23% was the most suitable for GMC of less than 40%. This study provides a real-time and cost-effective non-destructive GMC measurement using smartphones that enables on-farm prediction of harvest dates and facilitates the harvesting scheduling of agricultural machinery.
Subject(s)
Algorithms , Smartphone , Edible Grain , Machine Learning , Neural Networks, ComputerABSTRACT
BACKGROUND: Second primary cancer of the esophagus is frequent in head and neck patients, especially in high-risk populations, and has a great impact on the prognosis. Although Positron emission tomography (PET)/computed tomography (CT) scan is commonly conducted in head and neck patients, its ability to detect early esophageal cancer is limited. Narrow-band imaging endoscopy is an accurate and convenient technique for esophageal examination. We aimed to compare PET/CT scan and narrow-band imaging endoscopy for the detection of esophageal cancer in head and neck cancer patients. METHODS: From November 2015 to November 2018, all head and neck cancer patients who underwent both PET/CT scan and narrow-band imaging endoscopy at Changhua Christian Hospital were retrospectively enrolled. Descriptive statistics, receiver operating characteristic curve analysis, logistic regression analysis, independent Student's t-test, and Kaplan-Meier survival analysis were conducted with MedCalc Statistical Software. RESULTS: A total of 147 subjects were included in the analysis; suspicious esophageal lesions were identified by PET/CT scan in 8 (5.44%) and by narrow-band imaging in 35 (23.81%). The final pathologic diagnoses were esophageal squamous cell carcinoma in 10 and high-grade dysplasia in 5. The respective sensitivity, specificity, and area under the curve for detecting suspicious esophageal lesions were 33.33, 97.73%, and 0.655 for PET/CT scan, and 100.0, 84.85%, and 0.924 for narrow-band imaging endoscopy. Hypopharyngeal or laryngeal location of the primary head and neck cancer was the only risk factor for developing second primary esophageal cancer. CONCLUSIONS: PET/CT scan was inferior to narrow-band imaging endoscopy in detecting second primary esophageal cancer in head and neck cancer patients. In addition to PET/CT scan, narrow-band imaging endoscopy should be considered in head and neck patients at high risk for developing second primary esophageal cancer.
Subject(s)
Endoscopy, Digestive System , Esophageal Squamous Cell Carcinoma/diagnosis , Narrow Band Imaging , Positron Emission Tomography Computed Tomography , Adult , Aged , Aged, 80 and over , Disease Management , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/therapy , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Narrow Band Imaging/methods , Narrow Band Imaging/standards , Prognosis , ROC Curve , Retrospective Studies , Young AdultABSTRACT
Rice is one of the three major crops in the world and is the major crop in Asia. Climate change and water resource shortages may result in decreases in rice yields and possible food shortage crises. In this study, water-saving farming management was tested, and IOT field water level monitoring was used to regulate water inflow automatically. Plant height (PH) is an important phenotype to be used to determine difference in rice growth periods and yields using water-saving irrigation. An unmanned aerial vehicle (UAV) with an RGB camera captured sequential images of rice fields to estimate rice PH compared with PH measured on site for estimating rice growth stages. The test results, with two crop harvests in 2019, revealed that with adequate image calibration, the correlation coefficient between UAV-PH and field-PH was higher than 0.98, indicating that UAV images can accurately determine rice PH in the field and rice growth phase. The study demonstrated that water-saving farming is effective, decreasing water usage for the first and second crops of 2019 by 53.5% and 21.7%, respectively, without influencing the growth period and final yield. Coupled with an automated irrigation system, rice farming can be adaptive to water shortage situations.
Subject(s)
Crops, Agricultural , Oryza , Agricultural Irrigation , Agriculture , Asia , Remote Sensing TechnologyABSTRACT
BACKGROUND: Age, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not yet been examined. METHODS: This retrospective, cross-sectional study involved 3190 participants, including 207 participants (6.5%) with gallstones and 986 (30.9%) with metabolic syndrome. Participants were divided into four phenotypes according to metabolic syndrome and obesity status: 1378 participants were metabolically healthy and non-obese (MHNO); 826 were metabolically healthy but obese (MHO); 185 were metabolically abnormal but not obese (MANO); and 801 participants were metabolically abnormal and obese (MAO). RESULTS: The MAO and MANO phenotypes had more gallstones than the MHO and MHNO phenotypes, regardless of age (< 50 or ≥ 50 years old). Multivariate analyses showed that phenotype was an independent risk factor for gallstones in participants < 50 years old (odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.32-2.28). Younger participants also had a higher risk of gallstones in the MAO (OR = 5.41, 95% CI = 2.31-12.66), MANO (OR = 3.18, 95% CI = 0.86-11.75), and MHO (OR = 2.17, 95% CI = 0.90-5.22) phenotypes than the MHNO phenotype. CONCLUSIONS: Our retrospective results demonstrate an increased association of gallstones in younger people (< 50 years old) with metabolic syndrome and obesity.
Subject(s)
Age Factors , Gallstones/etiology , Metabolic Syndrome/complications , Obesity/complications , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Phenotype , Retrospective Studies , Risk FactorsABSTRACT
Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/physiopathology , Phaeophyceae/chemistry , Reproduction/drug effects , Xanthophylls/therapeutic use , Animals , Antioxidants/metabolism , Blood Glucose/metabolism , Cell Survival/drug effects , Diabetes Mellitus, Experimental/chemically induced , Disease Models, Animal , Inflammation Mediators/metabolism , Insulin/blood , Insulin Resistance , Kisspeptins/genetics , Kisspeptins/metabolism , Male , Malondialdehyde/metabolism , Mice , Niacinamide , Nitric Oxide/metabolism , Oxidative Stress/drug effects , RAW 264.7 Cells , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Receptors, Kisspeptin-1/genetics , Receptors, Kisspeptin-1/metabolism , Spermatozoa/drug effects , Spermatozoa/metabolism , Streptozocin , Suppressor of Cytokine Signaling 3 Protein/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , Testis/drug effects , Testis/pathology , Xanthophylls/pharmacologyABSTRACT
Anterior cruciate ligament (ACL) injury is one of the common musculoskeletal injuries. The most serious condition shall be managed by surgery, while the partial tear prefers conservative treatment, rehabilitation, exercise training, or platelet-rich plasma (PRP) injection. We describe the case of a 25-year-old female started to have right knee pain for a long time and the ACL partial tear was diagnosed through the magnetic resonance imaging (MRI). After three times of PRP injection through ultrasound guidance, the pain, instability, and enhancements of ACL tear in the postintervention MRI were decreased. This case confirms the effect of PRP combined with conservative treatment under the accuracy procedure and may provide another choice for the treatment of the ACL tear.
ABSTRACT
OBJECTIVES: To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. METHODS: Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. RESULTS: Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. CONCLUSIONS: When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Pain Measurement , Range of Motion, Articular/drug effects , Tennis Elbow/drug therapy , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Hand Strength , Humans , Injections, Intralesional , Male , Randomized Controlled Trials as Topic , Range of Motion, Articular/physiology , Severity of Illness Index , Taiwan , Tennis Elbow/diagnosis , Tennis Elbow/rehabilitation , Treatment OutcomeABSTRACT
How neuronal ensembles compute information is actively studied in early visual cortex. Much less is known about how local ensembles function in inferior temporal (IT) cortex, the last stage of the ventral visual pathway that supports visual recognition. Previous reports suggested that nearby neurons carry information mostly independently, supporting efficient processing (Barlow, 1961). However, others postulate that noise covariation effects may depend on network anisotropy/homogeneity and on how the covariation relates to representation. Do slow trial-by-trial noise covariations increase or decrease IT's object coding capability, how does encoding capability relate to correlational structure (i.e., the spatial pattern of signal and noise redundancy/homogeneity across neurons), and does knowledge of correlational structure matter for decoding? We recorded simultaneously from â¼80 spiking neurons in â¼1 mm(3) of macaque IT under light neurolept anesthesia. Noise correlations were stronger for neurons with correlated tuning, and noise covariations reduced object encoding capability, including generalization across object pose and illumination. Knowledge of noise covariations did not lead to better decoding performance. However, knowledge of anisotropy/homogeneity improved encoding and decoding efficiency by reducing the number of neurons needed to reach a given performance level. Such correlated neurons were found mostly in supragranular and infragranular layers, supporting theories that link recurrent circuitry to manifold representation. These results suggest that redundancy benefits manifold learning of complex high-dimensional information and that subsets of neurons may be more immune to noise covariation than others. SIGNIFICANCE STATEMENT: How noise affects neuronal population coding is poorly understood. By sampling densely from local populations supporting visual object recognition, we show that recurrent circuitry supports useful representations and that subsets of neurons may be more immune to noise covariation than others.
Subject(s)
Neurons/physiology , Temporal Lobe/cytology , Temporal Lobe/physiology , Visual Pathways/physiology , Visual Perception/physiology , Action Potentials/physiology , Animals , Anisotropy , Computer Simulation , Female , Generalization, Psychological , Macaca , Male , Photic Stimulation , Statistics as Topic , Support Vector Machine , Time FactorsABSTRACT
BACKGROUND & AIMS: In Taiwan, patients with chronic hepatitis C virus (HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection ± compensated cirrhosis. METHODS: In this multicentre, open-label, phase 3b (NCT02021643) study, 87 patients (n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were also collected. RESULTS: All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment-emergent adverse events (AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon. CONCLUSIONS: The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection.
Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Ribavirin/administration & dosage , Sofosbuvir/administration & dosage , Adult , Aged , Antiviral Agents/adverse effects , Drug Therapy, Combination , Female , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Humans , Liver Cirrhosis/virology , Male , Middle Aged , Ribavirin/adverse effects , Sofosbuvir/adverse effects , Taiwan , Treatment Outcome , Viral Load , Young AdultABSTRACT
BACKGROUND AND AIM: Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS: In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS: The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS: Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
Subject(s)
Benzimidazoles/administration & dosage , Carbamates/administration & dosage , Fluorenes/administration & dosage , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Sofosbuvir/administration & dosage , Adult , Aged , Drug Combinations , Female , Humans , Male , Middle Aged , Tablets , Taiwan , Treatment OutcomeABSTRACT
We evaluated second-line salvage therapy with adefovir + telbivudine (group 1), adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir followed by adefovir + telbivudine (group 3) in hepatitis B patients with an inadequate virologic response to lamivudine treatment. Simple linear regression analysis showed that for each additional month of treatment, the most significant reduction in viral load occurred in group 1 (HBV DNA [Log10 IU/mL]: group 1, -0.149; group 2, -0.081; group 3, -0.123). Generalized estimating equation analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels were 1.203 and 0.443 Log10 IU/mL higher in groups 2 and 3, respectively. Overall, a significant reduction in viral load (-0.060 Log10 IU/mL) was observed for each additional month of treatment. Adefovir + telbivudine treatment resulted in a significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted in a significant reduction in viral load (-0.050 Log10 IU/mL) compared to lamivudine treatment after the emergence of lamivudine resistance.