Published data for the epidemiology of idiopathic pulmonary fibrosis in the USA are scarce. We sought to estimate the incidence, prevalence, and mortality risk of idiopathic pulmonary fibrosis among ...US Medicare beneficiaries.
We used administrative claims from a 5% random sample of Medicare beneficiaries (aged 65 years and older) from the years 2000-11 as a data source. Idiopathic pulmonary fibrosis was defined by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. We estimated annual incidence and cumulative prevalence of idiopathic pulmonary fibrosis, median survival time of patients, and potential risk factors for diagnosis of idiopathic pulmonary fibrosis and death between 2001 and 2011. We also estimated incidence and prevalence using more restrictive algorithms for diagnosis.
The annual incidence of idiopathic pulmonary fibrosis in the Medicare population remained stable between 2001 and 2011, with an overall estimate of 93.7 cases per 100000 person-years (95% CI 91.9-95.4) across the study period. The annual cumulative prevalence increased steadily from 202.2 cases per 100000 people in 2001 to 494.5 cases per 100000 people in 2011. Among newly diagnosed patients with Medicare (mean age 79.4 years SD 7.2, 54% female, 91% white), the median survival time was 3.8 years (95% CI 3.5-3.8). Older age and male sex were associated with a higher incidence of disease and shorter survival time after diagnosis. Mortality risk was lower in patients diagnosed in more recent years (median survival time 3.3 years 95% CI 3.0-3.8 in 2001 vs 4.0 years 3.8-4.5 in 2007).
The incidence and prevalence of idiopathic pulmonary fibrosis in people aged 65 years and older in the USA are substantially higher than previously reported, and prevalence is increasing annually, even in the subgroups based on more restrictive algorithms for diagnosis. Patients with idiopathic pulmonary fibrosis aged 65 years and older were living longer in 2011 than they were 10 years before, which could partly account for the steady increase in prevalence.
Biogen Idec.
BackgroundThe programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade ...the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.MethodsPatients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.ResultsBetween May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.ConclusionsTislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration number NCT02407990.
Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung ...progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Extracorporeal shock wave therapy (ESWT) has been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a lack of objective evidence. We ...measured change of urinary biomarker levels in 25 patients with IC/BPS received ESWT or placebo once a week for 4 weeks. Urines were collected from participants at baseline, 4 and 12 weeks post treatment. A representative 41 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Symptom bother was assessed by O'Leary-Sant symptom scores (OSS), and visual analog scale (VAS) for pain. The ESWT group exhibited a significant reduction in the OSS and VAS compared to the placebo group 4 weeks post-treatment (P < 0.05), and the effects were persistent at 12 weeks. The difference in urinary markers change in ESWT versus placebo was P = 0.054 for IL4, P = 0.013 for VEGF, and P = 0.039 for IL9 at 4 weeks. The change of urine biomarker was not significant in other biomarkers or all the measured proteins at 12 weeks. The current data suggest that IL4, IL9, and VEGF mediation may be involved in its pathophysiologic mechanisms and response to LESW treatment.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
We investigated the relation between expression of sirtuin 5 (SIRT5) in osteoblastic cells and progression of apical periodontitis. The role of SIRT5 in hypoxia‐induced reactive oxygen ...species (ROS) formation and osteoblast apoptosis was also examined.
Materials and Methods
Progression of rat apical periodontitis was monitored by conventional radiography and microcomputed tomography. SIRT5 and oxidative stress biomarker 8‐OHdG in bone‐lining cells were assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling was used to demonstrate apoptosis. In primary human osteoblasts cultured under hypoxia, Western blot was used to analyze SIRT5 expression and cleavage of pro‐caspase 3 and poly(ADP‐ribose) polymerase (PARP). SIRT5 was overexpressed through lentiviral technique. ROS formation and mitochondrial membrane potential changes were assessed by MitoSOX‐Red and JC‐1 fluorescence, respectively. Immunofluorescence microscope was used to evaluate mitochondrial release of cytochrome c.
Results
In rat apical periodontitis, disease progression was accompanied by decreased expression of SIRT5, increased oxidative stress, and enhanced apoptosis in bone‐lining cells. SIRT5 was suppressed in cultured osteoblasts under hypoxia. SIRT5 overexpression ameliorated hypoxia‐enhanced ROS formation, mitochondrial depolarization, cytochrome c leakage, activation of caspase‐3, and PARP fragmentation.
Conclusions
SIRT5 is able to alleviate hypoxia‐enhanced osteoblast apoptosis. SIRT5 augmentation may have therapeutic potential for apical periodontitis.
Full text
Available for:
CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background An unscheduled return visit (URV) to the emergency department (ED) within 72-h is an indicator of ED performance. An unscheduled return revisit (URV) within 72-h was used to monitor ...adverse events and medical errors in a hospital quality improvement program. The study explores the potential factors that contribute to URV to the ED within 72-h and the unscheduled return revisit admission (URVA) in adults below 50 years old. Methods The case-control study enrolled 9483 URV patients during 2015-2020 in National Cheng-Kung University Hospital. URVA and URV non-admission (URVNA) patients were analyzed. The Gini impurity index was calculated by decision tree (DT) to split the variables capable of partitioning the groups into URVA and URVNA. Logistic regression is applied to calculate the odds ratio (OR) of candidate variables. The alpha level was set at 0.05. Results Among patients under the age of 50, the percentage of females in URVNA was 55.05%, while in URVA it was 53.25%. Furthermore, the average age of URVA patients was 38.20 + or - 8.10, which is higher than the average age of 35.19 + or - 8.65 observed in URVNA. The Charlson Comorbidity Index (CCI) of the URVA patients (1.59 + or - 1.00) was significantly higher than that of the URVNA patients (1.22 + or - 0.64). The diastolic blood pressure (DBP) of the URVA patients was 85.29 + or - 16.22, which was lower than that of the URVNA (82.89 + or - 17.29). Severe triage of URVA patients is 21.1%, which is higher than the 9.7% of URVNA patients. The decision tree suggests that the factors associated with URVA are "severe triage," "CCI higher than 2," "DBP less than 86.5 mmHg," and "age older than 34 years". These risk factors were verified by logistic regression and the OR of CCI was 2.42 (1.50-3.90), the OR of age was 1.84 (1.50-2.27), the OR of DBP less than 86.5 was 0.71 (0.58-0.86), and the OR of severe triage was 2.35 (1.83-3.03). Conclusions The results provide physicians with a reference for discharging patients and could help ED physicians reduce the cognitive burden associated with the diagnostic errors and stress. Keywords: Charlson comorbidity index, Emergency department, Unscheduled revisit, Admission
There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic ...analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared it with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, therefore camelid HEV, which is genotype 7, might infect human beings. Our finding links consumption of camel-derived food products to post-transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents.
The proton exchange membrane water electrolyzer (PEMWE) requires a high operating voltage for hydrogen production to accelerate the decomposition of hydrogen molecules so that the PEMWE ages or ...fails. According to the prior findings of this R&D team, temperature and voltage can influence the performance or aging of PEMWE. As the PEMWE ages inside, the nonuniform flow distribution results in large temperature differences, current density drops, and runner plate corrosion. The mechanical stress and thermal stress resulting from pressure distribution nonuniformity will induce the local aging or failure of PEMWE. The authors of this study used gold etchant for etching, and acetone was used for the lift-off part. The wet etching method has the risk of over-etching, and the cost of the etching solution is also higher than that of acetone. Therefore, the authors of this experiment adopted a lift-off process. Using the flexible seven-in-one (voltage, current, temperature, humidity, flow, pressure, oxygen) microsensor developed by our team, after optimized design, fabrication, and reliability testing, it was embedded in PEMWE for 200 h. The results of our accelerated aging test prove that these physical factors affect the aging of PEMWE.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The proton battery has facilitated a new research direction for technologies related to fuel cells and energy storage. Our R&D team has developed a prototype of a proton battery stack, but there are ...still problems to be solved, such as leakage and unstable power generation. Moreover, it is unlikely that the multiple important physical parameters inside the proton battery stack can be measured accurately and simultaneously. At present, external or single measurements represent the bottleneck, yet the multiple important physical parameters (oxygen, hydrogen, voltage, current, temperature, flow, and humidity) are interrelated and have a significant impact on the performance, life, and safety of the proton battery stack. This research uses micro-electro-mechanical systems (MEMS) technology to develop a micro oxygen sensor and integrates the six-in-one microsensor that our R&D team previously developed in order to improve sensor output and facilitate overall operation by redesigning the incremental mask and having this co-operate with a flexible board for sensor back-end integration, completing the development of a flexible seven-in-one (oxygen, hydrogen, voltage, current, temperature, flow, and humidity) microsensor.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The voltage, current, temperature, humidity, pressure, flow, and hydrogen in the high-pressure proton exchange membrane water electrolyzer (PEMWE) can influence its performance and life. For example, ...if the temperature is too low to reach the working temperature of the membrane electrode assembly (MEA), the performance of the high-pressure PEMWE cannot be enhanced. However, if the temperature is too high, the MEA may be damaged. In this study, the micro-electro-mechanical systems (MEMS) technology was used to innovate and develop a high-pressure-resistant flexible seven-in-one (voltage, current, temperature, humidity, pressure, flow, and hydrogen) microsensor. It was embedded in the upstream, midstream, and downstream of the anode and cathode of the high-pressure PEMWE and the MEA for the real-time microscopic monitoring of internal data. The aging or damage of the high-pressure PEMWE was observed through the changes in the voltage, current, humidity, and flow data. The over-etching phenomenon was likely to occur when this research team used wet etching to make microsensors. The back-end circuit integration was unlikely to be normalized. Therefore, this study used lift-off process to further stabilize the quality of the microsensor. In addition, the PEMWE is more prone to aging and damage under high pressure, so its material selection is very important.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
