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1.
Int Urogynecol J ; 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38856754

INTRODUCTION AND HYPOTHESIS: Catheterization is a common treatment for postpartum urinary retention (PUR); however, its application before diagnosis of PUR remains unclear. The aim was to give an overview of the existing literature on the effectiveness and safety of intrapartum or postpartum catheterization in the prevention of PUR. METHODS: This scoping review followed a methodological framework. PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, WanFang, the China Science and Technology Journal Database, and the China Biomedical Literature Database were searched from the inception of each database to 21 May 2023. RESULTS: The search revealed 16 studies examining three different catheterization methodologies, including 12 intrapartum studies. Ten studies concluded that intrapartum or postpartum catheterization prevented PUR, two of which were only for overt or covert PUR. In 4 out of 13 experimental studies, no significant difference was found: one for intrapartum catheterization versus routine nursing, the other for intrapartum or postpartum intermittent versus indwelling catheterization. However, one found that postpartum disposable catheterization after ineffective targeted care reduced the incidence of PUR compared with indwelling catheterization. One out of the 3 case-control studies concluded that prenatal catheterization ≥2 times was a risk factor for PUR. CONCLUSIONS: Based on the findings in this scoping review, catheterization prior to the diagnosis of PUR appears to play a role in preventing PUR and is safe. Preliminary evidence is accumulating on the effectiveness of three types of catheterization methods in preventing PUR, but more comprehensive studies are needed to establish these findings.

2.
Adv Mater ; : e2311845, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720198

Sweat gland (SwG) regeneration is crucial for the functional rehabilitation of burn patients. In vivo chemical reprogramming that harnessing the patient's own cells in damaged tissue is of substantial interest to regenerate organs endogenously by pharmacological manipulation, which could compensate for tissue loss in devastating diseases and injuries, for example, burns. However, achieving in vivo chemical reprogramming is challenging due to the low reprogramming efficiency and an unfavorable tissue environment. Herein, this work has developed a functionalized proteinaceous nanoformulation delivery system containing prefabricated epidermal growth factor structure for on-demand delivery of a cocktail of seven SwG reprogramming components to the dermal site. Such a chemical reprogramming system can efficiently induce the conversion of epidermal keratinocytes into SwG myoepithelial cells, resulting in successful in situ regeneration of functional SwGs. Notably, in vivo chemical reprogramming of SwGs is achieved for the first time with an impressive efficiency of 30.6%, surpassing previously reported efficiencies. Overall, this proteinaceous nanoformulation provides a platform for coordinating the target delivery of multiple pharmacological agents and facilitating in vivo SwG reprogramming by chemicals. This advancement greatly improves the clinical accessibility of in vivo reprogramming and offers a non-surgical, non-viral, and cell-free strategy for in situ SwG regeneration.

3.
Burns Trauma ; 12: tkae003, 2024.
Article En | MEDLINE | ID: mdl-38699464

Sebaceous glands (SGs), as holocrine-secreting appendages, lubricate the skin and play a central role in the skin barrier. Large full-thickness skin defects cause overall architecture disruption and SG loss. However, an effective strategy for SG regeneration is lacking. Organoids are 3D multicellular structures that replicate key anatomical and functional characteristics of in vivo tissues and exhibit great potential in regenerative medicine. Recently, considerable progress has been made in developing reliable procedures for SG organoids and existing SG organoids recapitulate the main morphological, structural and functional features of their in vivo counterparts. Engineering approaches empower researchers to manipulate cell behaviors, the surrounding environment and cell-environment crosstalk within the culture system as needed. These techniques can be applied to the SG organoid culture system to generate functionally more competent SG organoids. This review aims to provide an overview of recent advancements in SG organoid engineering. It highlights some potential strategies for SG organoid functionalization that are promising to forge a platform for engineering vascularized, innervated, immune-interactive and lipogenic SG organoids. We anticipate that this review will not only contribute to improving our understanding of SG biology and regeneration but also facilitate the transition of the SG organoid from laboratory research to a feasible clinical application.

4.
J Wound Care ; 33(Sup4): S25-S32, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38573950

OBJECTIVE: This study aimed to evaluate the effectiveness of podiatrists in preventing diabetic foot ulcers (DFUs) in China. METHOD: The study was a prospective investigation. A total of 300 patients were enrolled from May 2016 to May 2018 in Handan Central Hospital, China. All patients who participated in this study had been diagnosed with type 2 diabetes, according to the International Classification of Diseases (ICD-10). All participants underwent our survey, which included basic patient data and information about DFUs. The patients were followed for one year, during which time they received appropriate intervention from podiatrists, including lifestyle guidance, callus resection, tinea grinding and ingrown nail correction. At the end of the year all the patients were surveyed again. The data before and after the year were statistically compared. RESULTS: The results showed that the incidence of DFUs in patients with diabetes was significantly decreased after one year of intervention from podiatrists (20.7% versus 6.7%, p<0.001). Additionally, there was a negative correlation between the number of intervention visits and the number of DFU occurrences (Spearman correlation coefficient: -0.496, p<0.001). Furthermore, we found that 68 patients with a history of DFUs or amputation had an obviously reduced incidence of DFUs after intervention by a podiatrist (89.7% versus 27.9%, p<0.001). We also investigated other foot risk factors in all participants, such as limb neuropathy (76.3%), lower extremity vascular disease (65.7%) and foot paralysis (43.7%). CONCLUSION: The results of this study help in understanding the situation of patients with diabetes in China and to prove that standardised podiatrist intervention has an important role in inhibiting the occurrence and development of DFUs.


Diabetes Mellitus, Type 2 , Diabetic Foot , Foot Ulcer , Humans , Diabetic Foot/epidemiology , Diabetic Foot/prevention & control , Diabetic Foot/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Incidence , Prospective Studies , Hospitals
6.
BMC Pregnancy Childbirth ; 23(1): 761, 2023 Oct 28.
Article En | MEDLINE | ID: mdl-37898733

BACKGROUND: Postpartum urinary incontinence substantially impacts the psychophysical well-being of women. The influencing factors contributing to postpartum urinary incontinence remain a subject of contention in clinical investigation. By elucidating the factors contributing to postpartum urinary incontinence, more efficacious interventions for laboring women can be devised. Consequently, this review endeavored to scrutinize the repercussions of maternal postpartum urinary incontinence to furnish empirical references for the clinical advancement of preventive strategies. METHOD: The investigation employed bibliographic databases: Embase, PubMed, Web of Science, Cochrane Library, CBM, VIP, CNKI, and Wan Fang Data for article retrieval. A comprehensive consideration of all study designs was undertaken during the examination of the effects of postpartum urinary incontinence. The temporal limitation was set at all articles prior to February 2023. Studies incorporated laboring mothers experiencing normative labor and parturition. A total of 28,303 women were encompassed in the reviewed investigations. RESULTS: A total of 5,915 putative citations were identified, from which 32 articles were selected for evaluating the effects of postpartum urinary incontinence. Meta-analyses revealed that the incidence of postpartum urinary incontinence was 26% [95%CI: (21% ~ 30%)]. Twelve pivotal variables were identified to influence postpartum urinary incontinence: cesarean delivery, vaginal delivery, age ≥ 35 years, multiparty (number of deliveries ≥ 2), neonatal weight > 4 kg, perineal dystonia, antecedents of urological incontinence-related pathology, maternal pre-conception BMI ≥ 24 kg/m^2, perineal laceration, instrumental parturition, historical pelvic surgical procedures, and protracted second stage of labor. Among these, cesarean delivery was identified as a protective factor against postpartum urinary incontinence. CONCLUSION: The study corroborated that anamnestic factors pertinent to urinary incontinence, vaginal parturitions, and neonates with a weight exceeding 4 kg serve as significant risk factors for postpartum urinary incontinence. Cesarean delivery emerged as a protective factor against postpartum urinary incontinence. Based on the prevalence of postpartum urinary incontinence, proactive intervention is requisite to mitigate the risk of postpartum urinary incontinence in postpartum women possessing these risk factors. TRIAL REGISTRATION: CRD42023412096.


Postpartum Period , Urinary Incontinence , Adult , Female , Humans , Pregnancy , Delivery, Obstetric/adverse effects , Delivery, Obstetric/methods , Parturition , Prevalence , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology
7.
Medicine (Baltimore) ; 102(41): e35399, 2023 Oct 13.
Article En | MEDLINE | ID: mdl-37832117

BACKGROUND: To compare the effect of different noninvasive external therapies of traditional Chinese medicine (TCM) on the prevention of postpartum urinary retention (PUR) using a network meta-analysis (NMA). METHODS: A search of the China National Knowledge Infrastructure, WanFangDate, VIP, China Biomedical Literature Database, PubMed, The Cochrane Library, Embase, and Web of Science databases were reviewed for related randomized controlled trials dated between database inception and December 31, 2022, on the prevention of PUR by noninvasive TCM. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies; then, a NMA was performed using Revman5.3 software, State13.1 software, and frequency methodology. RESULTS: In total, 16 studies involving 3637 cases of parturients and 9 types of noninvasive TCM external treatments were incorporated into the NMA. The NMA results show that based on routine nursing, in terms of reducing the incidence of urinary retention, acupoint compressing combined with auricular acupressure is ranked first, followed by acupoint hot compress, acupoint massage combined with auricular acupressure, Yin-Yang therapy, acupoint massage, auricular acupressure, acupoint compressing, and routine nursing. In terms of urination time, acupoint compressing combined with auricular acupressure ranked first, followed by acupoint massage combined with auricular acupressure, acupoint electrical stimulation, acupoint compressing, TCM heating therapy, acupoint massage, auricular acupressure, and routine nursing. In terms of reducing residual urine volume after the first urination, acupoint compressing combined with auricular acupressure was ranked first, followed by auricular acupressure, acupoint compressing, acupoint massage, TCM heating therapy, and routine nursing. CONCLUSION: Current evidence shows that acupoint compressing combined with auricular acupressure may be the best noninvasive TCM treatment for preventing PUR based on routine nursing; however, further high-quality clinical randomized controlled trials are needed for validation and support.


Acupressure , Acupuncture Therapy , Urinary Retention , Humans , Female , Pregnancy , Medicine, Chinese Traditional , Network Meta-Analysis , Urinary Retention/etiology , Urinary Retention/prevention & control , Acupuncture Therapy/methods , Acupressure/methods , Delivery, Obstetric
8.
Materials (Basel) ; 16(19)2023 Sep 28.
Article En | MEDLINE | ID: mdl-37834584

Many bridge structural components are subjected to repetitive vehicle load and temperature gradient action. The resulting cyclic tensile stresses within the structures could cause premature fatigue failure of concrete, dramatically impairing structural components' durability and sustainability. Although substantial knowledge of fatigue properties on low-strength pavement concrete and high-strength structural concrete has been obtained, research on the most widely used normal-grade ordinary concrete in bridge engineering is still ongoing. Therefore, a four-point bending fatigue test of 97 C50 concrete specimens under a constant amplitude sinusoidal wave was conducted in the laboratory, the flexural fatigue behavior of plain and reinforced concrete specimens was studied, and the cyclic deformation evolution of concrete under fatigue loading was obtained. The empirical fatigue S-N equations of concrete with a failure probability p of 0.1~0.5 were derived through statistical analysis of the test results. The fatigue life of the tested specimens exhibited a two-parameter Weibull distribution. In addition to the maximum stress level Smax, the stress ratio R is also a key factor affecting the flexural fatigue life of concrete N. The semi-logarithmic and logarithmic equations were almost identical at the tested stress levels, the latter predicting longer fatigue life for Smax < 0.70. The restraining effect from steel reinforcement slightly lengthened the concrete's fatigue cracking initiation life. The insight into concrete flexural fatigue properties from this study not only contributes to a better understanding of structural concrete, but also provides a basis for the practical evaluation of concrete or composite bridge decks.

10.
Burns Trauma ; 11: tkad027, 2023.
Article En | MEDLINE | ID: mdl-37397511

Background: Promoting rapid wound healing with functional recovery of all skin appendages is the main goal of regenerative medicine. So far current methodologies, including the commonly used back excisional wound model (BEWM) and paw skin scald wound model, are focused on assessing the regeneration of either hair follicles (HFs) or sweat glands (SwGs). How to achieve de novo appendage regeneration by synchronized evaluation of HFs, SwGs and sebaceous glands (SeGs) is still challenging. Here, we developed a volar skin excisional wound model (VEWM) that is suitable for examining cutaneous wound healing with multiple-appendage restoration, as well as innervation, providing a new research paradigm for the perfect regeneration of skin wounds. Methods: Macroscopic observation, iodine-starch test, morphological staining and qRT-PCR analysis were used to detect the existence of HFs, SwGs, SeGs and distribution of nerve fibres in the volar skin. Wound healing process monitoring, HE/Masson staining, fractal analysis and behavioral response assessment were performed to verify that VEWM could mimic the pathological process and outcomes of human scar formation and sensory function impairment. Results: HFs are limited to the inter-footpads. SwGs are densely distributed in the footpads, scattered in the IFPs. The volar skin is richly innervated. The wound area of the VEWM at 1, 3, 7 and 10 days after the operation is respectively 89.17% ± 2.52%, 71.72% ± 3.79%, 55.09 % ± 4.94% and 35.74% ± 4.05%, and the final scar area accounts for 47.80% ± 6.22% of the initial wound. While the wound area of BEWM at 1, 3, 7 and 10 days after the operation are respectively 61.94% ± 5.34%, 51.26% ± 4.89%, 12.63% ± 2.86% and 6.14% ± 2.84%, and the final scar area accounts for 4.33% ± 2.67% of the initial wound. Fractal analysis of the post-traumatic repair site for VEWM vs human was performed: lacunarity values, 0.040 ± 0.012 vs 0.038 ± 0.014; fractal dimension values, 1.870 ± 0.237 vs 1.903 ± 0.163. Sensory nerve function of normal skin vs post-traumatic repair site was assessed: mechanical threshold, 1.05 ± 0.52 vs 4.90 g ± 0.80; response rate to pinprick, 100% vs 71.67% ± 19.92%, and temperature threshold, 50.34°C ± 3.11°C vs 52.13°C ± 3.54°C. Conclusions: VEWM closely reflects the pathological features of human wound healing and can be applied for skin multiple-appendages regeneration and innervation evaluation.

11.
Signal Transduct Target Ther ; 8(1): 116, 2023 03 14.
Article En | MEDLINE | ID: mdl-36918530

The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. The great leaps in cellular rejuvenation prove that ageing is not a one-way street, and many rejuvenative interventions have emerged to delay and even reverse the ageing process. Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies. Here, we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation, and the targeted cells and core mechanisms involved in this process. Then, we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation. Various rejuvenation methods also provide insights for treating specific ageing-related diseases, including cellular reprogramming, the removal of senescence cells (SCs) and suppression of senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune rejuvenation and heterochronic transplantation, etc. The potential applications of rejuvenation therapy also extend to cancer treatment. Finally, we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology. Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.


Epigenesis, Genetic , Rejuvenation , Rejuvenation/physiology , Cellular Reprogramming/genetics
12.
Materials (Basel) ; 15(13)2022 Jun 25.
Article En | MEDLINE | ID: mdl-35806616

Concrete tensile properties usually govern the fatigue cracking of structural components such as bridge decks under repetitive loading. A fatigue life reliability analysis of commonly used ordinary cement concrete is desirable. As fatigue is affected by many interlinked factors whose effect is nonlinear, a unanimous consensus on the quantitative measurement of these factors has not yet been achieved. Benefiting from its unique self-learning ability and strong generalization capability, the Bayesian regularized backpropagation neural network (BR-BPNN) was proposed to predict concrete behavior in tensile fatigue. A total of 432 effective data points were collected from the literature, and an optimal model was determined with various combinations of network parameters. The average relative impact value (ARIV) was constructed to evaluate the correlation between fatigue life and its influencing parameters (maximum stress level Smax, stress ratio R, static strength f, failure probability P). ARIV results were compared with other factor assessment methods (weight equation and multiple linear regression analyses). Using BR-BPNN, S-N curves were obtained for the combinations of R = 0.1, 0.2, 0.5; f = 5, 6, 7 MPa; P = 5%, 50%, 95%. The tensile fatigue results under different testing conditions were finally compared for compatibility. It was concluded that Smax had the most significant negative effect on fatigue life; and the degree of influence of R, P, and f, which positively correlated with fatigue life, decreased successively. ARIV was confirmed as a feasible way to analyze the importance of parameters and could be recommended for future applications. It was found that the predicted logarithmic fatigue life agreed well with the test results and conventional data fitting curves, indicating the reliability of the BR-BPNN model in predicting concrete tensile fatigue behavior. These probabilistic fatigue curves could provide insights into fatigue test program design and fatigue evaluation. Since the overall correlation coefficient between the prediction and experimental results reached 0.99, the experimental results of plain concrete under flexural tension, axial tension, and splitting tension could be combined in future analyses. Besides utilizing the valuable fatigue test data available in the literature, this work provided evidence of the successful application of BR-BPNN on concrete fatigue prediction. Although a more accurate and comprehensive method was derived in the current study, caution should still be exercised when utilizing this method.

13.
Mil Med Res ; 9(1): 13, 2022 03 29.
Article En | MEDLINE | ID: mdl-35351192

BACKGROUND: Large skin defects severely disrupt the overall skin structure and can irreversibly damage sweat glands (SG), thus impairing the skin's physiological function. This study aims to develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages, which may provide a promising method to obtain desirable cell types for the functional repair and regeneration of damaged skin. METHODS: The expression of the SG markers cytokeratin 5 (CK5), cytokeratin 10 (CK10), cytokeratin 18 (CK18), carcino-embryonic antigen (CEA), aquaporin 5 (AQP5) and α-smooth muscle actin (α-SMA) was assessed with quantitative PCR (qPCR), immunofluorescence and flow cytometry. Calcium activity analysis was conducted to test the function of induced SG-like cells (iSGCs). Mouse xenograft models were also used to evaluate the in vivo regeneration of iSGCs. BALB/c nude mice were randomly divided into a normal group, SGM treatment group and iSGC transplantation group. Immunocytochemical analyses and starch-iodine sweat tests were used to confirm the in vivo regeneration of iSGCs. RESULTS: EDA overexpression drove HDF conversion into iSGCs in SG culture medium (SGM). qPCR indicated significantly increased mRNA levels of the SG markers CK5, CK18 and CEA in iSGCs, and flow cytometry data demonstrated (4.18 ± 0.04)% of iSGCs were CK5 positive and (4.36 ± 0.25)% of iSGCs were CK18 positive. The addition of chemical cocktails greatly accelerated the SG fate program. qPCR results revealed significantly increased mRNA expression of CK5, CK18 and CEA in iSGCs, as well as activation of the duct marker CK10 and luminal functional marker AQP5. Flow cytometry indicated, after the treatment of chemical cocktails, (23.05 ± 2.49)% of iSGCs expressed CK5+ and (55.79 ± 3.18)% of iSGCs expressed CK18+, respectively. Calcium activity analysis indicated that the reactivity of iSGCs to acetylcholine was close to that of primary SG cells [(60.79 ± 7.71)% vs. (70.59 ± 0.34)%, ns]. In vivo transplantation experiments showed approximately (5.2 ± 1.1)% of the mice were sweat test positive, and the histological analysis results indicated that regenerated SG structures were present in iSGCs-treated mice. CONCLUSION: We developed a SG reprogramming strategy to generate functional iSGCs from HDFs by using the single factor EDA in combination with SGM and small molecules. The generation of iSGCs has important implications for future in situ skin regeneration with SG restoration.


Cellular Reprogramming , Sweat Glands , Animals , Fibroblasts , Humans , Mice , Mice, Nude , Regeneration , Sweat Glands/metabolism
14.
Adv Sci (Weinh) ; 8(22): e2103079, 2021 11.
Article En | MEDLINE | ID: mdl-34569165

Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin-A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.


Keratinocytes/metabolism , Organoids/metabolism , Regeneration/physiology , Sweat Glands/metabolism , Tissue Engineering/methods , Wound Healing/physiology , Adolescent , Adult , Animals , Disease Models, Animal , Epidermis/metabolism , Female , Humans , Keratinocytes/cytology , Male , Mice , Mice, Nude , Organoids/cytology , Sweat Glands/cytology , Young Adult
15.
Front Immunol ; 12: 668758, 2021.
Article En | MEDLINE | ID: mdl-34122427

Wound healing is a multi-step process that includes multiple cellular events such as cell proliferation, cell adhesion, and chemotactic response as well as cell apoptosis. Accumulating studies have documented the significance of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) signaling in wound repair and regeneration. However, the molecular mechanism of regeneration is not clear. This review describes various types of tissue regeneration that CXCR4 participates in and how the efficiency of regeneration is increased by CXCR4 overexpression. It emphasizes the pleiotropic effects of CXCR4 in regeneration. By delving into the specific molecular mechanisms of CXCR4, we hope to provide a theoretical basis for tissue engineering and future regenerative medicine.


Chemokine CXCL12/metabolism , Receptors, CXCR4/metabolism , Regeneration , Skin/metabolism , Wound Healing , Animals , Apoptosis , Cell Proliferation , Humans , Inflammation Mediators/metabolism , Ligands , Receptors, CXCR4/genetics , Signal Transduction , Skin/pathology
17.
Article En | MEDLINE | ID: mdl-18922744

A highly sensitive and specific LC-MS method was developed and validated for the quantification of digoxin in human plasma and urine using d5-dihydrodigoxin as internal standard (IS). The assay procedure involved extraction of digoxin and IS from human plasma with chloroform-isopropanol (95:5, v/v). Chromatogrphic separation was achieved on a Spherisorb ODS2 column using a gradient mobile phase with 5 mmol/L ammonium acetate in water with 1% acetic acid and acetonitrile. The mass spectrometer was operated in the selected ion monitoring mode using the respective [M+K](+) ions, m/z 819.4 for digoxin and m/z 826.4 for IS. The method was proved to be accurate and precise at linearity range of 0.12-19.60 ng/mL in plasma with a correlation coefficient (r(2)) of >or=0.9968 and 1.2-196.0 ng/mL in urine. The limit of quantification achieved with this method was 0.12 ng/mL in plasma and 1.2 ng/mL in urine. The intra- and inter-assay precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was successfully applied to a pharmacokinetic study in human volunteers following intravenous administration of digoxin.


Chromatography, Liquid/methods , Digoxin/blood , Digoxin/urine , Spectrometry, Mass, Electrospray Ionization/methods , Digoxin/administration & dosage , Digoxin/pharmacokinetics , Drug Stability , Humans , Infusions, Intravenous , Reference Standards , Reproducibility of Results , Sensitivity and Specificity
18.
J Clin Pharmacol ; 47(10): 1268-76, 2007 Oct.
Article En | MEDLINE | ID: mdl-17906160

A randomized, dose-escalating study evaluated the pharmacokinetics of single and multiple oral doses of pirfenidone, a promising antifibrotic agent, in 48 healthy Chinese volunteers. The effects of sex and food on the pharmacokinetics of pirfenidone were also evaluated. Pharmacokinetics was determined from serial blood samples obtained up to 12 hours after administration of single 200-, 400-, or 600-mg doses of pirfenidone and after multiple doses of 400 mg administrated 3 times daily (tid). Plasma levels of pirfenidone and areas under the curve were found to be proportional to dose. Pirfenidone was rapidly absorbed (t(max) = 0.33-1 hours) and cleared (t((1/2)) = 2-2.5 hours). Pharmacokinetic parameters after multiple doses were similar to those after single doses. Food had a significant effect (P < .01) on the extent of absorption (AUC(0-infinity) = 37.4 +/- 15.4 mg x h/L [fed] vs 46.6 +/- 16.8 mg x h/L [fasted]), rate of absorption was considerably (P < .001) prolonged (t(max) = 1.5 +/- 0.4 hours [fed] vs 0.7 +/- 0.2 hours [fasted]), and peak concentrations were significantly (P < .001) decreased (C(max) = 9.2 +/- 2.9 mg/L [fed] vs 13.0 +/- 1.8 mg/L [fasted]). No significant sex differences were noted for pharmacokinetic variables. Pirfenidone was well tolerated. These results support a tid regimen of pirfenidone for the management of idiopathic pulmonary fibrosis. Concomitant intake of food will reduce the rate and extent (about 20%) of absorption, which is associated with better tolerability of pirfenidone.


Food-Drug Interactions , Pyridones/administration & dosage , Pyridones/pharmacokinetics , Adult , Area Under Curve , China , Female , Humans , Male , Pulmonary Fibrosis/drug therapy , Pyridones/blood , Pyridones/therapeutic use , Sex Factors
19.
Chin Med J (Engl) ; 117(6): 856-61, 2004 Jun.
Article En | MEDLINE | ID: mdl-15198887

BACKGROUND: A voluntary procedure for reporting adverse drug reactions (ADRs) was formally put in place in 1989. However, only a small proportion of ADR reports are actually forwarded to the national monitoring center. To identify the reasons for underreporting, the authors investigated the awareness and attitudes of healthcare professionals (doctors, nurses, and administrators) toward the ADR system in China. In addition, the authors sought to formulate approaches to improve the current ADR reporting system. METHODS: Structured interviews were carried out in 16 hospitals selected from 27 municipal hospitals in Wuhan, Hubei Province, China. A questionnaire survey of a stratified random sample of approximately 15% of healthcare professionals in each selected hospital was conducted during February to March 2003. RESULTS: The response rate of this survey was 85%. One thousand six hundred and fifty-three questionnaires were used in the final analysis. Only 2.7% of the healthcare professionals had a correct understanding to the definition of ADR. Eighty-nine point two percent of the healthcare professionals had encountered ADRs. Ninety-four percent of them were aware of the need to report these to the ADR monitoring center. However, only 28.5% of doctors, 22.8% of nurses, and 29.7% of administrators actually submitted a report. For the most part, they reported ADRs to the hospital pharmacy (66.0%), to other departments in the hospital (72.5%), and to the pharmaceutical industry (23.0%), rather than to the national monitoring center (2.9%) or regional monitoring center (9.5%). Severe or rare ADRs and ADRs to new products were generally perceived to be significant enough to report. Sixty-two point one percent of the healthcare professionals had encountered ADRs, yet not reported them to anybody. The major reasons for not reporting included no knowledge of the reporting procedure (71.4%), unavailability of the reporting center mailing address (67.9%), unavailability of the ADR report form (60.4%), lack of knowledge of the existence of a national ADR reporting system (52.2%), and belief that the ADR in question was already well known (44.1%). CONCLUSIONS: Healthcare professionals in Wuhan, China have little basic knowledge of ADR and of the voluntary reporting system. The main reasons for underreporting were lack of basic knowledge about ADRs and the voluntary reporting procedure. Education and training of healthcare professionals is needed to improve the current ADR reporting system.


Adverse Drug Reaction Reporting Systems/trends , Attitude of Health Personnel , China , Health Knowledge, Attitudes, Practice , Hospital Administrators , Humans , Interviews as Topic , Nurses , Physicians , Surveys and Questionnaires
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 25(10): 894-7, 2004 Oct.
Article Zh | MEDLINE | ID: mdl-15631751

OBJECTIVE: To investigate the knowledge and attitudes of healthcare professionals (doctors, nurses and administrators) to adverse drug reactions (ADR) in Wuhan city and to identify the reasons for under-reporting. METHODS: Structured interviews were carried out in Wuhan, Hubei province. Questionnaire survey to approximately 15% of the medical practitioners selected from 16 hospitals, was conducted during the period from February to March 2003. RESULTS: Only 2.7% of the interviewees knew the definition of adverse drug reactions. 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers. The major reasons for not reporting included: ignorant about the requirement and the reporting process of ADR (71.4%); address of the reporting agency and Forms unavailable (67.9%, 60.4%); unaware of the existence of a national ADR reporting system (52.2%); needless to report as the ADR being too well known (44.1%). They mainly reported an ADR to the hospital pharmacy or other departments, or to the pharmaceutical administration. Education, training and developing new institutions were ways to improve the reporting system. CONCLUSIONS: Our results showed that healthcare professionals had little knowledge on the basic ADR knowledge. The main reasons for underreporting were related to factors on reporting process, address of related centers and unavailable of the Forms. Education and training to doctors and nurses to enhance the awareness of administrators were the ways to improve the reporting system.


Attitude of Health Personnel , Drug-Related Side Effects and Adverse Reactions , Health Knowledge, Attitudes, Practice , Adverse Drug Reaction Reporting Systems , China , Female , Humans , Male , Practice Patterns, Physicians' , Surveys and Questionnaires
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