[Needle-free injection--science fiction or comeback of an almost forgotten drug delivery system?].

PubMed

Ziegler, Andreas

2007-08-01

The first to create a "needle-free injector" was the American anesthetist Robert A. Hingson, 65 year ago. Since that time those devices underwent a changeful history. In 1986 an outbreak of hepatitis B among patients receiving injections from a needle-free multiple-use-nozzle injector was documented and related to the use of the injector device. Due to such risk of transmission of infection with these reusable devices, their application has been restricted. In 1998 the WHO recommended that only conventional needles and syringes should be used for immunization until safe needle-free injectors are identified through independent safety testing. Since needle-free injection has shown numerous advantages in comparison to conventional injection, new systems were developed that combine the advantages of needle-free injection with sufficient safety in mass vaccination programs. As an alternative to this early injector type, the disposable-cartridge injectors were developed. The newest research field in the area of the needle-free injection systems opened with the development of powder injectors, in which the drug preparation is no longer a suspension or solution, but a powdered solid. This injector type using powder formulations shows a number of advantages in comparison with the conventional needle/syringe injection technique as well as towards the liquid jet injectors. Due to this new kind of injectors the comeback of the needle-free injection technique in large-scale vaccination programs of the WHO seems reasonable and within reach.

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

PubMed

Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

2015-04-15

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

Design optimisation of a nanofluid injection system for LOCA events in a nuclear power plant

NASA Astrophysics Data System (ADS)

Călimănescu, I.; Stan, L. C.; Velcea, D. D.

2016-08-01

The safety issues inside a Nuclear Power Plant (NPP) are encompassing their capacity to ensure the heat sink, meaning the capacity of the systems to release the heat from the rector to the environment. The nanofluids having good heat transfer properties, are recommended to be used in such applications. The paper is solving the following scenario: considering the Safety Injection tank and the Nanofluid injection Tank, and considering the Nanofluid injection Tank filled with a 10% alumina-water nanofluid, how can we select the best design of the connecting point between the pipes of the SIT and the Nanofluid Tank and the pressures inside of any of these tanks in order to have the biggest density of nanoparticles leaving the tanks toward the cold leg. In conclusion the biggest influence over the rate of disposal of the nanofluid inside ECCS is that of the pressure inside the SIT followed in order by the injection pipe diameter and the pressure inside the nanofluid tank. The optimum balance of these three design parameters may be reached following the procedure shown in this paper.

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment.

PubMed

Liu, Jia; Qi, Chao; Tao, Kaixiong; Zhang, Jinxiang; Zhang, Jian; Xu, Luming; Jiang, Xulin; Zhang, Yunti; Huang, Lei; Li, Qilin; Xie, Hongjian; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

2016-03-01

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wichman, K.; Tsao, J.; Mayfield, M.

The regulatory application of leak before break (LBB) for operating and advanced reactors in the U.S. is described. The U.S. Nuclear Regulatory Commission (NRC) has approved the application of LBB for six piping systems in operating reactors: reactor coolant system primary loop piping, pressurizer surge, safety injection accumulator, residual heat removal, safety injection, and reactor coolant loop bypass. The LBB concept has also been applied in the design of advanced light water reactors. LBB applications, and regulatory considerations, for pressurized water reactors and advanced light water reactors are summarized in this paper. Technology development for LBB performed by the NRCmore » and the International Piping Integrity Research Group is also briefly summarized.« less

[Establishment of model of traditional Chinese medicine injections post-marketing safety monitoring].

PubMed

Guo, Xin-E; Zhao, Yu-Bin; Xie, Yan-Ming; Zhao, Li-Cai; Li, Yan-Feng; Hao, Zhe

2013-09-01

To establish a nurse based post-marketing safety surveillance model for traditional Chinese medicine injections (TCMIs). A TCMIs safety monitoring team and a research hospital team engaged in the research, monitoring processes, and quality control processes were established, in order to achieve comprehensive, timely, accurate and real-time access to research data, to eliminate errors in data collection. A triage system involving a study nurse, as the first point of contact, clinicians and clinical pharmacists was set up in a TCM hospital. Following the specified workflow involving labeling of TCM injections and using improved monitoring forms it was found that there were no missing reports at the ratio of error was zero. A research nurse as the first and main point of contact in post-marketing safety monitoring of TCM as part of a triage model, ensures that research data collected has the characteristics of authenticity, accuracy, timeliness, integrity, and eliminate errors during the process of data collection. Hospital based monitoring is a robust and operable process.

A New Partial Reconfiguration-Based Fault-Injection System to Evaluate SEU Effects in SRAM-Based FPGAs

NASA Astrophysics Data System (ADS)

Sterpone, L.; Violante, M.

2007-08-01

Modern SRAM-based field programmable gate array (FPGA) devices offer high capability in implementing complex system. Unfortunately, SRAM-based FPGAs are extremely sensitive to single event upsets (SEUs) induced by radiation particles. In order to successfully deploy safety- or mission-critical applications, designer need to validate the correctness of the obtained designs. In this paper we describe a system based on partial-reconfiguration for running fault-injection experiments within the configuration memory of SRAM-based FPGAs. The proposed fault-injection system uses the internal configuration capabilities that modern FPGAs offer in order to inject SEU within the configuration memory. Detailed experimental results show that the technique is orders of magnitude faster than previously proposed ones.

Regulatory Concerns on the In-Containment Water Storage System of the Korean Next Generation Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Hyung-Joon; Lee, Jae-Hun; Bang, Young-Seok

2002-07-15

The in-containment water storage system (IWSS) is a newly adopted system in the design of the Korean Next Generation Reactor (KNGR). It consists of the in-containment refueling water storage tank, holdup volume tank, and cavity flooding system (CFS). The IWSS has the function of steam condensation and heat sink for the steam release from the pressurizer and provides cooling water to the safety injection system and containment spray system in an accident condition and to the CFS in a severe accident condition. With the progress of the KNGR design, the Korea Institute of Nuclear Safety has been developing Safety andmore » Regulatory Requirements and Guidances for safety review of the KNGR. In this paper, regarding the IWSS of the KNGR, the major contents of the General Safety Criteria, Specific Safety Requirements, Safety Regulatory Guides, and Safety Review Procedures were introduced, and the safety review items that have to be reviewed in-depth from the regulatory viewpoint were also identified.« less

A System for Integrated Reliability and Safety Analyses

NASA Technical Reports Server (NTRS)

Kostiuk, Peter; Shapiro, Gerald; Hanson, Dave; Kolitz, Stephan; Leong, Frank; Rosch, Gene; Coumeri, Marc; Scheidler, Peter, Jr.; Bonesteel, Charles

1999-01-01

We present an integrated reliability and aviation safety analysis tool. The reliability models for selected infrastructure components of the air traffic control system are described. The results of this model are used to evaluate the likelihood of seeing outcomes predicted by simulations with failures injected. We discuss the design of the simulation model, and the user interface to the integrated toolset.

Uncovering high rates of unsafe injection equipment reuse in rural Cameroon: validation of a survey instrument that probes for specific misconceptions

PubMed Central

2011-01-01

Background Unsafe reuse of injection equipment in hospitals is an on-going threat to patient safety in many parts of Africa. The extent of this problem is difficult to measure. Standard WHO injection safety assessment protocols used in the 2003 national injection safety assessment in Cameroon are problematic because health workers often behave differently under the observation of visitors. The main objective of this study is to assess the extent of unsafe injection equipment reuse and potential for blood-borne virus transmission in Cameroon. This can be done by probing for misconceptions about injection safety that explain reuse without sterilization. These misconceptions concern useless precautions against cross-contamination, i.e. "indirect reuse" of injection equipment. To investigate whether a shortage of supply explains unsafe reuse, we compared our survey data against records of purchases. Methods All health workers at public hospitals in two health districts in the Northwest Province of Cameroon were interviewed about their own injection practices. Injection equipment supply purchase records documented for January to December 2009 were compared with self-reported rates of syringe reuse. The number of HIV, HBV and HCV infections that result from unsafe medical injections in these health districts is estimated from the frequency of unsafe reuse, the number of injections performed, the probability that reused injection equipment had just been used on an infected patient, the size of the susceptible population, and the transmission efficiency of each virus in an injection. Results Injection equipment reuse occurs commonly in the Northwest Province of Cameroon, practiced by 44% of health workers at public hospitals. Self-reported rates of syringe reuse only partly explained by records on injection equipment supplied to these hospitals, showing a shortage of syringes where syringes are reused. Injection safety interventions could prevent an estimated 14-336 HIV infections, 248-661 HBV infections and 7-114 HCV infections each year in these health districts. Conclusions Injection safety assessments that probe for indirect reuse may be more effective than observational assessments. The autodisable syringe may be an appropriate solution to injection safety problems in some hospitals in Cameroon. Advocacy for injection safety interventions should be a public health priority. PMID:21299899

Induced seismicity closed-form traffic light system for actuarial decision-making during deep fluid injections.

PubMed

Mignan, A; Broccardo, M; Wiemer, S; Giardini, D

2017-10-19

The rise in the frequency of anthropogenic earthquakes due to deep fluid injections is posing serious economic, societal, and legal challenges to many geo-energy and waste-disposal projects. Existing tools to assess such problems are still inherently heuristic and mostly based on expert elicitation (so-called clinical judgment). We propose, as a complementary approach, an adaptive traffic light system (ATLS) that is function of a statistical model of induced seismicity. It offers an actuarial judgement of the risk, which is based on a mapping between earthquake magnitude and risk. Using data from six underground reservoir stimulation experiments, mostly from Enhanced Geothermal Systems, we illustrate how such a data-driven adaptive forecasting system could guarantee a risk-based safety target. The proposed model, which includes a linear relationship between seismicity rate and flow rate, as well as a normal diffusion process for post-injection, is first confirmed to be representative of the data. Being integrable, the model yields a closed-form ATLS solution that is both transparent and robust. Although simulations verify that the safety target is consistently ensured when the ATLS is applied, the model from which simulations are generated is validated on a limited dataset, hence still requiring further tests in additional fluid injection environments.

An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback.

PubMed

Chang, Yen-Chi; Berry-Pusey, Brittany; Yasin, Rashid; Vu, Nam; Maraglia, Brandon; Chatziioannou, Arion X; Tsao, Tsu-Chin

2015-08-01

This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system.

Safety of ultrashort-term sit with pollen allergoids adjuvanted by monophosphoryl lipid A: a prospective Italian survey.

PubMed

Crivellaro, M; Senna, G E; Pappacoda, A; Vanzelli, R; Spacal, B; Marchi, G; Recchia, G; Makatsori, M

2011-03-01

A 3-year prospective post marketing survey on the safety of the recently developed ultrashort pre-seasonal subcutaneous immunotherapy (uSCIT-MPL4) with pollen allergoids adjuvanted with monophosphoryl lipid A was performed. A total of 510 patients received uSCIT-MPL4, 61% for grass, 35.7% for birch, 13.2% for parietaria and 3% for other pollens (ragweed, mugwort, and olive). A total of 3308 injections were given and the mean duration of uSCIT-MPL-4 was 2.3 years. Overall, only 7 slight systemic reactions (SR) were observed in 510 patients (1.37%) and 2.11/1000 injections suggesting that this treatment is even safer than traditional depot injection SIT.

ASIL determination for motorbike's Electronics Throttle Control System (ETCS) mulfunction

NASA Astrophysics Data System (ADS)

Zaman Rokhani, Fakhrul; Rahman, Muhammad Taqiuddin Abdul; Ain Kamsani, Noor; Sidek, Roslina Mohd; Saripan, M. Iqbal; Samsudin, Khairulmizam; Khair Hassan, Mohd

2017-11-01

Electronics Throttle Control System (ETCS) is the principal electronic unit in all fuel injection engine motorbike, augmenting the engine performance efficiency in comparison to the conventional carburetor based engine. ETCS is regarded as a safety-critical component, whereby ETCS malfunction can cause unintended acceleration or deceleration event, which can be hazardous to riders. In this study, Hazard Analysis and Risk Assessment, an ISO26262 functional safety standard analysis has been applied on motorbike's ETCS to determine the required automotive safety integrity level. Based on the analysis, the established automotive safety integrity level can help to derive technical and functional safety measures for ETCS development.

Strategies for safe injections.

PubMed Central

Battersby, A.; Feilden, R.; Stoeckel, P.; Da Silva, A.; Nelson, C.; Bass, A.

1999-01-01

In 1998, faced with growing international concern, WHO set out an approach for achieving injection safety that encompassed all elements from patients' expectations and doctors' prescribing habits to waste disposal. This article follows that lead and describes the implications of the approach for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system, and choose injection technologies that fit their circumstances. PMID:10680247

Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine triad protein D vaccine.

PubMed

Bologa, Monica; Kamtchoua, Thierry; Hopfer, Robert; Sheng, Xiaohua; Hicks, Bryony; Bixler, Garvin; Hou, Victor; Pehlic, Vildana; Yuan, Tao; Gurunathan, Sanjay

2012-12-14

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae. To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations. This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)-adjuvanted PcpA (25 μg) or PhtD-PcpA (10 μg each), participants in the main study received AH-adjuvanted PcpA (25 μg), AH-adjuvanted PhtD-PcpA (10, 25, or 50 μg each), unadjuvanted PhtD-PcpA (25 μg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA). Six adults 18-50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose-escalating comparison, a plateau effect at the 25 μg dose was observed as measured by geometric mean concentrations and by fold increases. Promising safety profiles and immunogenicity of these monovalent and bivalent protein vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov registry no. NCT01444339). Copyright © 2012 Elsevier Ltd. All rights reserved.

Efficiency and safety of subconjunctival injection of anti-VEGF agent - bevacizumab - in treating dry eye.

PubMed

Jiang, Xiaodan; Lv, Huibin; Qiu, Weiqiang; Liu, Ziyuan; Li, Xuemin; Wang, Wei

2015-01-01

Dry eye is a chronic inflammatory ocular surface disease with high prevalence. The current therapies for dry eye remain to be unspecific and notcomprehensive. This study aims to explore safety and efficacy of a novel treatment - subconjunctival injection of bevacizumab - in dry eye patients. Sixty-four eyes of 32 dry eye patients received subconjunctival injection of 100 μL 25 mg/mL bevacizumab. Dry eye symptoms, signs (corrected visual acuity, intraocular pressure, conjunctival vascularity, corneal staining, tear break-up time, Marx line score, and blood pressure), and conjunctival impression cytology were evaluated 3 days before and 1 week, 1 month, and 3 months after injection. Significant improvements were observed in dry eye symptoms, tear break-up time, and conjunctival vascularization area at all the visits after injection compared to the baseline (P<0.05). The density of the goblet cell increased significantly at 1 month and 3 months after injection (P<0.05). There was no visual and systemic threat observed in any patient. Subconjunctival injection of 100 μL 25 mg/mL bevacizumab is a safe and efficient treatment for ocular surface inflammation of dry eye disease.

Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

PubMed Central

Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

2011-01-01

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

77 FR 16036 - Determination That CITANEST (Prilocaine Hydrochloride) Injection, 1%, 2%, and 3%, and CITANEST...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... marketing for reasons other than safety or effectiveness. ANDAs that refer to CITANEST (prilocaine HCl... Hydrochloride) Injection, 4%, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food... (prilocaine HCl) Injection, 4%, were not withdrawn from sale for reasons of safety or effectiveness. This...

Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats.

PubMed

Yokoo, T; Kamimura, K; Suda, T; Kanefuji, T; Oda, M; Zhang, G; Liu, D; Aoyagi, Y

2013-08-01

The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml(-1)) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone.

Assessment of injection safety in Ha Dong General Hospital, Hanoi, in 2012.

PubMed

Van Tuong, Phan; Phuong, Tran Thi Minh; Anh, Bui Thi My; Nguyen, Trang Huyen Thi

2017-01-01

Background : Injection is one of the most frequently used medical methods to introduce drugs or other substances into the body for purposes of treatment or prevention. Unsafe injection can cause adverse outcomes, such as abscess and anaphylactic shock, and increases the risk of blood-borne transmission of viruses to patients and health care workers, as well as the community. Recognizing the importance of injection safety, in 2000 the Vietnamese Ministry of Health (MOH) collaborated with the Vietnam Nurses Association to launch the "Safe injection" program throughout the country, including Hanoi. Methods : This cross-sectional study, combining quantitative and qualitative analysis, was conducted from February to August 2012 in Ha Dong General Hospital using a structured questionnaire and observation checklist. The target population of the study was 109 nurses working in clinical departments and 436 injections were observed. Results : The percentage of nurses who are familiar with injection safety standards was found to be 82.6%. The proportion of practical injections that met the 23 standards of injection safety set by the MOH amounted to 22.2%. The factors related to safe injection practice of nurses who were younger age group (OR=3.1; p<0.05) and fewer number of years working as a nurse (OR=2.8; p<0.05). Conclusions : While nurses have high level of knowledge about safe injections but a small proportion actually practiced. Experience may not always guarantee safe practices.  Injection safety training should be regularly imparted upon all categories of nurses.

Safety of immunization injections in Africa: not simply a problem of logistics.

PubMed Central

Dicko, M.; Oni, A. Q.; Ganivet, S.; Kone, S.; Pierre, L.; Jacquet, B.

2000-01-01

In 1995, the WHO Regional Office for Africa launched a logistics project to address the four main areas of immunization logistics: the cold chain, transport, vaccine supply and quality, and the safety of injections in the countries of the region. The impact of this logistic approach on immunization injection safety was evaluated through surveys of injection procedures and an analysis of the injection materials (e.g. sterilizable or disposable syringes) chosen by the Expanded Programme on Immunization (EPI) and those actually seen to be used. Re-use of injection materials without sterilization, accidental needle-stick injuries among health care workers, and injection-related abscesses in patients were common in countries in the WHO African Region. Few health centres used time-steam saturation-temperature (TST) indicators to check the quality of sterilization and, in many centres, the injection equipment was boiled instead of being steam sterilized. Facilities for the proper disposal of used materials were rarely present. Although the official EPI choice was to use sterilizable equipment, use of a combination of sterilizable and disposable equipment was observed in the field. Unsafe injection practices in these countries were generally due to a failure to integrate nursing practices and public awareness with injection safety issues, and an absence of the influence of EPI managers on health care service delivery. Holistic rather than logistic approaches should be adopted to achieve safe injections in immunization, in the broader context of promoting safe vaccines and safety of all injections. PMID:10743280

Injection safety practices in a main referral hospital in Northeastern Nigeria.

PubMed

Gadzama, G B; Bawa, S B; Ajinoma, Z; Saidu, M M; Umar, A S

2014-01-01

No adherence of safe injection policies remains a major challenge, and, worldwide, annually, it leads to 21 million new hepatitis B cases and 260,000 HIV infection cases. This descriptive observational survey was conducted to determine the level of adherence to universal precaution for safe injection practices in the hospital. The study units were selected using a simple random sampling of injection services provider/phlebotomist in 27 units/wards of the hospital. The study instruments were observation checklist and interviewer administered questionnaires. EPI info (version 3.5.2) software was used for data entry and generation of descriptive statistics was done with units of analysis (units/wards) on injection safety practices of health workers, availability of logistics and supplies, and disposal methods. Only 33.3% of the units (95% CI, 16-54) had non-sharps infectious healthcare waste of any type inside containers specific for non-sharps infectious waste and 17 (77.3%) of the observed therapeutic injections were prepared on a clean, dedicated table or tray, where contamination of the equipment with blood, body fluids, or dirty swabs was unlikely. Absence of recapping of needles was observed in 11 (50.0%) units giving therapeutic injections. Only 7.4% of units surveyed had separate waste containers for infectious non-sharps. This study depicts poor knowledge and a practice of injection safety, inadequate injection safety supplies, and non-compliance to injection safety policy and guidelines.

Feasibilty of in utero DNA vaccination following naked gene transfer into pig fetal muscle: transgene expression, immunity and safety.

PubMed

Rinaldi, Monica; Signori, Emanuela; Rosati, Paolo; Cannelli, Giorgio; Parrella, Paola; Iannace, Enrico; Monego, Giovanni; Ciafrè, Silvia Anna; Farace, Maria Giulia; Iurescia, Sandra; Fioretti, Daniela; Rasi, Guido; Fazio, Vito Michele

2006-05-22

The high toll of death among first-week infants is due to infections occurring at the end of pregnancy, during birth or by breastfeeding. This problem significantly concerns industrialized countries also. To prevent the typical "first-week infections", a vaccine would be protective as early as at the birth. In utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. We have already published results of a 2-year follow-up showing long-term safety, protective antibody titers at birth and long-term immune memory, following intramuscular in utero anti-HBV DNA immunization in 90-days pig fetuses. We have now analyzed further parameters of short-term safety. Two different reporter genes were injected in the thigh muscles of 90-days fetuses. At 8 days following DNA injection, we found high-level of transgenes expression in all injected fetuses. A step gradient of expression from the area of injection was observed with both reporter genes. CMV promoter/enhancer produced higher levels of expression compared to SV40 promoter/enhancer. Moreover, no evidence of local or systemic flogistic alterations or fetal malformations, mortality or haemorrhage following intramuscular injection were observed. A single anti-HBV s-antigen DNA immunization in 90-days fetuses supported protective antibody levels in all immunized newborns, lasting at least up to 4 months after birth. Our report further sustains safety and efficacy of intramuscular in utero naked gene transfer and immunization. This approach may support therapeutic or prophylactic procedure in many early life-threatening pathologic conditions.

Assessment of injection safety in Ha Dong General Hospital, Hanoi, in 2012

PubMed Central

Van Tuong, Phan; Phuong, Tran Thi Minh; Anh, Bui Thi My; Nguyen, Trang Huyen Thi

2017-01-01

Background: Injection is one of the most frequently used medical methods to introduce drugs or other substances into the body for purposes of treatment or prevention. Unsafe injection can cause adverse outcomes, such as abscess and anaphylactic shock, and increases the risk of blood-borne transmission of viruses to patients and health care workers, as well as the community. Recognizing the importance of injection safety, in 2000 the Vietnamese Ministry of Health (MOH) collaborated with the Vietnam Nurses Association to launch the “Safe injection” program throughout the country, including Hanoi. Methods: This cross-sectional study, combining quantitative and qualitative analysis, was conducted from February to August 2012 in Ha Dong General Hospital using a structured questionnaire and observation checklist. The target population of the study was 109 nurses working in clinical departments and 436 injections were observed. Results: The percentage of nurses who are familiar with injection safety standards was found to be 82.6%. The proportion of practical injections that met the 23 standards of injection safety set by the MOH amounted to 22.2%. The factors related to safe injection practice of nurses who were younger age group (OR=3.1; p<0.05) and fewer number of years working as a nurse (OR=2.8; p<0.05). Conclusions: While nurses have high level of knowledge about safe injections but a small proportion actually practiced. Experience may not always guarantee safe practices.  Injection safety training should be regularly imparted upon all categories of nurses. PMID:29188014

10 CFR Appendix E to Part 50 - Emergency Planning and Preparedness for Production and Utilization Facilities

Code of Federal Regulations, 2011 CFR

2011-01-01

... could communicate with a safety system. In this case, appropriate isolation devices would be required at..., feedwater flow, and reactor power; (2) Safety injection: Reactor core isolation cooling flow, high-pressure... data points identified in the ERDS Data Point Library 9 (site specific data base residing on the ERDS...

10 CFR Appendix E to Part 50 - Emergency Planning and Preparedness for Production and Utilization Facilities

Code of Federal Regulations, 2010 CFR

2010-01-01

... could communicate with a safety system. In this case, appropriate isolation devices would be required at..., feedwater flow, and reactor power; (2) Safety injection: Reactor core isolation cooling flow, high-pressure... data points identified in the ERDS Data Point Library 9 (site specific data base residing on the ERDS...

Westinghouse Small Modular Reactor passive safety system response to postulated events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, M. C.; Wright, R. F.

2012-07-01

The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (>225 MWe) integral pressurized water reactor. This paper is part of a series of four describing the design and safety features of the Westinghouse SMR. This paper focuses in particular upon the passive safety features and the safety system response of the Westinghouse SMR. The Westinghouse SMR design incorporates many features to minimize the effects of, and in some cases eliminates the possibility of postulated accidents. The small size of the reactor and the low power density limits the potential consequences of an accident relative to a large plant. Themore » integral design eliminates large loop piping, which significantly reduces the flow area of postulated loss of coolant accidents (LOCAs). The Westinghouse SMR containment is a high-pressure, compact design that normally operates at a partial vacuum. This facilitates heat removal from the containment during LOCA events. The containment is submerged in water which also aides the heat removal and provides an additional radionuclide filter. The Westinghouse SMR safety system design is passive, is based largely on the passive safety systems used in the AP1000{sup R} reactor, and provides mitigation of all design basis accidents without the need for AC electrical power for a period of seven days. Frequent faults, such as reactivity insertion events and loss of power events, are protected by first shutting down the nuclear reaction by inserting control rods, then providing cold, borated water through a passive, buoyancy-driven flow. Decay heat removal is provided using a layered approach that includes the passive removal of heat by the steam drum and independent passive heat removal system that transfers heat from the primary system to the environment. Less frequent faults such as loss of coolant accidents are mitigated by passive injection of a large quantity of water that is readily available inside containment. An automatic depressurization system is used to reduce the reactor pressure in a controlled manner to facilitate the passive injection. Long-term decay heat removal is accomplished using the passive heat removal systems augmented by heat transfer through the containment vessel to the environment. The passive injection systems are designed so that the fuel remains covered and effectively cooled throughout the event. Like during the frequent faults, the passive systems provide effective cooling without the need for ac power for seven days following the accident. Connections are available to add additional water to indefinitely cool the plant. The response of the safety systems of the Westinghouse SMR to various initiating faults has been examined. Among them, two accidents; an extended station blackout event, and a LOCA event have been evaluated to demonstrate how the plant will remain safe in the unlikely event that either should occur. (authors)« less

Safer injections following a new national medicine policy in the public sector, Burkina Faso 1995 – 2000

PubMed Central

Logez, Sophie; Hutin, Yvan; Somda, Paul; Thuault, Jérôme; Holloway, Kathleen

2005-01-01

Background The common failure of health systems to ensure adequate and sufficient supplies of injection devices may have a negative impact on injection safety. We conducted an assessment in April 2001 to determine to which extent an increase in safe injection practices between 1995 and 2000 was related to the increased access to injection devices because of a new essential medicine policy in Burkina Faso. Methods We reviewed outcomes of the new medicine policy implemented in1995. In April 2001, a retrospective programme review assessed the situation between 1995 and 2000. We visited 52 health care facilities where injections had been observed during a 2000 injection safety assessment and their adjacent operational public pharmaceutical depots. Data collection included structured observations of available injection devices and an estimation of the proportion of prescriptions including at least one injection. We interviewed wholesaler managers at national and regional levels on supply of injection devices to public health facilities. Results Fifty of 52 (96%) health care facilities were equipped with a pharmaceutical depot selling syringes and needles, 37 (74%) of which had been established between 1995 and 2000. Of 50 pharmaceutical depots, 96% had single-use 5 ml syringes available. At all facilities, patients were buying syringes and needles out of the depot for their injections prescribed at the dispensary. While injection devices were available in greater quantities, the proportion of prescriptions including at least one injection remained stable between 1995 (26.5 %) and 2000 (23.8 %). Conclusion The implementation of pharmaceutical depots next to public health care facilities increased geographical access to essential medicines and basic supplies, among which syringes and needles, contributing substantially to safer injection practices in the absence of increased use of therapeutic injections. PMID:16364178

Assessment of the safety of injection practices and injection-related procedures in family health units and centers in Alexandria.

PubMed

Elhoseeny, Taghareed A; Mourad, Juidan K

2014-08-01

The Safe Injection Global Network (SIGN) developed an intervention strategy for reducing overuse of injections and promoting the administration of safe injections. Tool C--Revised is designed to assess the safety of the most common procedures that puncture the skin within health services. The aim of the study was to assess injection safety within the primary healthcare facilities in Alexandria using Tool C--Revised. A total of 45 family health units and centers in Alexandria were selected by proportional allocation from the eight regions of Alexandria. The Tool C--Revised of the WHO was used for observation of the entire facility, injection practices and injection-related procedures, and sterilization practices. Interview of different health providers and immediate supervisor of injections was carried out. Indicators that reflect risk included: deficiency of alcohol-based hand rub for cleansing hands (13.3%), compliance with hand wash before preparing a procedure (56.9% before injection practices, 61.3% before phlebotomy, and 67.6% before lancet puncture), and wearing a new pair of gloves before new procedures (48.6% before injection practices, 9.7% for phlebotomy, 11.8% for lancet puncture, and 80% for both intravenous injections and infusions). Enough disposable equipment in all facilities for at least 2 weeks dependent on the statement of the average numbers of procedures per week was shown. Only 38% of the providers had received training regarding injection safety in the last 2 years and 62.5% had completed their three doses of hepatitis B vaccine. Only 42.2% of staffs who handled healthcare waste had access to heavy gloves. Indicators related to injection and injection-related practices that reflect risk to patients include deficiency of alcohol-based hand rub tools, nonadherence to hand hygiene before preparing an injection, and inadequate adherence to using a clean barrier when opening a glass ampule and use of gloves. Indicators that may reflect risk to patients and providers include inadequate injection safety training and incomplete hepatitis B vaccination of healthcare providers. Indicators that may reflect risk to providers include nonadherence to safety precautions related to injection practices, such as inadequate access to heavy gloves by staff handling healthcare waste.

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review.

PubMed

Cañas, Fernando; Möller, Hans-Jürgen

2010-09-01

Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP). Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency. RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI. Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Development of CNG direct injection (CNGDI) clean fuel system for extra power in small engine

NASA Astrophysics Data System (ADS)

Ali, Yusoff; Shamsudeen, Azhari; Abdullah, Shahrir; Mahmood, Wan Mohd Faizal Wan

2012-06-01

A new design of fuel system for CNG engine with direct injection (CNGDI) was developed for a demonstration project. The development of the fuel system was done on the engine with cylinder head modifications, for fuel injector and spark plug openings included in the new cylinder head. The piston was also redesigned for higher compression ratio. The fuel rails and the regulators are also designed for the direct injection system operating at higher pressure about 2.0 MPa. The control of the injection timing for the direct injectors are also controlled by the Electronic Control Unit specially designed for DI by another group project. The injectors are selected after testing with the various injection pressures and spray angles. For the best performance of the high-pressure system, selection is made from the tests on single cylinder research engine (SCRE). The components in the fuel system have to be of higher quality and complied with codes and standards to secure the safety of engine for high-pressure operation. The results of the CNGDI have shown that better power output is produced and better emissions were achieved compared to the aspirated CNG engine.

Material Gradients in Oxygen System Components Improve Safety

NASA Technical Reports Server (NTRS)

Forsyth, Bradley S.

2011-01-01

Oxygen system components fabricated by Laser Engineered Net Shaping (TradeMark) (LENS(TradeMark)) could result in improved safety and performance. LENS(TradeMark) is a near-net shape manufacturing process fusing powdered materials injected into a laser beam. Parts can be fabricated with a variety of elemental metals, alloys, and nonmetallic materials without the use of a mold. The LENS(TradeMark) process allows the injected materials to be varied throughout a single workpiece. Hence, surfaces exposed to oxygen could be constructed of an oxygen-compatible material while the remainder of the part could be one chosen for strength or reduced weight. Unlike conventional coating applications, a compositional gradient would exist between the two materials, so no abrupt material boundary exists. Without an interface between dissimilar materials, there is less tendency for chipping or cracking associated with thermal-expansion mismatches.

Study of status of safe injection practice and knowledge regarding injection safety among primary health care workers in Baglung district, western Nepal.

PubMed

Gyawali, Sudesh; Rathore, Devendra S; Kc, Bhuvan; Shankar, P Ravi

2013-01-03

Unsafe injection practices and injection overuse are widespread in developing countries harming the patient and inviting risks to the health care workers. In Nepal, there is a dearth of documented information about injection practices so the present study was carried out: a) to determine whether the selected government health facilities satisfy the conditions for safe injections in terms of staff training, availability of sterile injectable equipment and their proper disposal after use and b) to assess knowledge and attitudes of healthcare workers in these health care facilities with regard to injection safety. A descriptive cross-sectional mixed type (qualitative and quantitative) survey was carried out from 18th May to 16th June 2012. In-depth interviews with the in-charges were conducted using a semi-structured questionnaire. Observation of the health facilities using a structured observation tool was done. The data were analysed manually by summarizing, tabulating and presenting in various formats. The in-charges (eight males, two females) who participated in the study ranged in age from 30 to 50 years with a mean age of 37.8 years. Severe infection followed by pain was the most important cause for injection use with injection Gentamicin being most commonly prescribed. New single use (disposable) injections and auto-disable syringes were used to inject curative drugs and vaccines respectively. Sufficient safety boxes were also supplied to dispose the used syringe. All health care workers had received full course of Hepatitis B vaccine and were knowledgeable about at least one pathogen transmitted through unsafe injection practices. Injection safety management policy and waste disposal guideline was not available for viewing in any of the facilities. The office staff who disposed the bio-medical wastes did so without taking any safety measures. Moreover, none of these staff had received any formal training in waste management. Certain safe injection practices were noticed in the studied health care facilities but there remain a number of grey areas where unsafe practices still persists placing patient and health workers at risk of associated hazards. Training concentrating on injection safety, guidelines to dispose biomedical waste and monitoring of the activity is needed.

Study of status of safe injection practice and knowledge regarding injection safety among primary health care workers in Baglung district, western Nepal

PubMed Central

2013-01-01

Background Unsafe injection practices and injection overuse are widespread in developing countries harming the patient and inviting risks to the health care workers. In Nepal, there is a dearth of documented information about injection practices so the present study was carried out: a) to determine whether the selected government health facilities satisfy the conditions for safe injections in terms of staff training, availability of sterile injectable equipment and their proper disposal after use and b) to assess knowledge and attitudes of healthcare workers in these health care facilities with regard to injection safety. Methodology A descriptive cross-sectional mixed type (qualitative and quantitative) survey was carried out from 18th May to 16th June 2012. In-depth interviews with the in-charges were conducted using a semi-structured questionnaire. Observation of the health facilities using a structured observation tool was done. The data were analysed manually by summarizing, tabulating and presenting in various formats. Results The in-charges (eight males, two females) who participated in the study ranged in age from 30 to 50 years with a mean age of 37.8 years. Severe infection followed by pain was the most important cause for injection use with injection Gentamicin being most commonly prescribed. New single use (disposable) injections and auto-disable syringes were used to inject curative drugs and vaccines respectively. Sufficient safety boxes were also supplied to dispose the used syringe. All health care workers had received full course of Hepatitis B vaccine and were knowledgeable about at least one pathogen transmitted through unsafe injection practices. Injection safety management policy and waste disposal guideline was not available for viewing in any of the facilities. The office staff who disposed the bio-medical wastes did so without taking any safety measures. Moreover, none of these staff had received any formal training in waste management. Conclusions Certain safe injection practices were noticed in the studied health care facilities but there remain a number of grey areas where unsafe practices still persists placing patient and health workers at risk of associated hazards. Training concentrating on injection safety, guidelines to dispose biomedical waste and monitoring of the activity is needed. PMID:23286907

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT.

PubMed

Chhablani, Jay; Narayanan, Raja; Mathai, Annie; Yogi, Rohit; Stewart, Michael

2016-06-01

To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration. Eligible eyes with choroidal neovascularization secondary to age-related macular degeneration each received a single intravitreal injection of ziv-aflibercept. Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injection, and International Society for Clinical Electrophysiology of Vision standard electroretinography was performed at baseline and Day 30. Primary outcome measures were safety parameters that included signs of clinical and electroretinographic toxicity. Secondary outcome measures included changes in best-corrected visual acuity and central subfield thickness. Twelve eyes of 12 patients were treated. None of the patients complained of blurred vision, ocular pain, or bulbar injection at any of the follow-up visits, nor was intraocular inflammation noted. There were no significant differences in implicit times, "a" and "b" wave amplitudes, or b/a ratios at 1 month when compared with baseline (P = 0.4). None of the patients experienced serious ocular or systemic adverse events. Mean best-corrected visual acuity improved only slightly at 30 days (LogMAR 0.45 ± 0.31 [Snellen equivalent: 20/60]) compared with baseline (LogMAR 0.37 ± 0.24 [Snellen equivalent: 20/50]; P = 0.51). Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

[Developing traditional Chinese medicine injection is the need for curing sickness to save patients].

PubMed

He, Ping; Li, Feng-Jie; Li, Lian-da; Li, Yi-Kui

2017-03-01

Safety issues of traditional Chinese medicine injections has been heated debate. There are two diametrically opposed views: it should be used reasonable and developed healthily or be forbidden to use. Some people have many misunderstandings and prejudices about the safety of traditional Chinese medicine injections. Compared with western medicine,traditional Chinese medicine has its own particularity. Traditional Chinese medicine has complex components. Its research and clinical application is different from western medicine. Adverse reactions of traditional Chinese medicine injections are related to many factors,such as a large number of irrational use,blind use of traditional Chinese medicine injections and western medicine injections,counterfeit and substandard drugs,incorrect methods of intravenous infusion,toxicity of supplementary materials,drug ingredients. Developing traditional Chinese medicine injection is the need for curing sickness to save patients. The purposeful, targeted, organized and planned systematic research of traditional Chinese medicine injections should be strengthened,especially the safety of traditional Chinese medicine. Strengthen supervision and control of rational drug use.Strengthen the examination and approval,supervision and management of all aspects to ensure the safety of patients. Copyright© by the Chinese Pharmaceutical Association.

[Strategy of constructing post-market integral evaluation system of traditional Chinese medicine injection].

PubMed

Zhang, Xiao-Yu; Wang, Yan-Ping; Lin, Li-Kai; Shang, Hong-Cai; Wang, Yong-Yan

2017-08-01

As an important representative of modern Chinese medicine, traditional Chinese medicine (TCM) injzection has become an indispensable part of the Chinese medicine industry. However, its development is now restricted by the bottleneck of insufficient core competitiveness, low-level research and production, even injection quality and the safe use are not guaranteed. Thus, it is urgent to reevaluate post-marketing TCM injection generally and to make secondary development. Under current circumstances, taking major brands which have good clinical and market foundation, as well as research value, as the main subject of cultivation and evaluation is an important approach to innovative development of TCM injection industry. Unlike oral proprietary Chinese medicine, the cultivatation of major brands of TCM injection needs higher technical support, quality standards and more timely feedback. Therefore, a post-market integral evaluation system adaptive to TCM injection is required. This article discussed some key points on the construction of a post-market integral evaluation system of TCM injection in three levels： optimizing evaluation methods, building synergistic innovation platforms which combine the medical research institutions and pharmaceutical enterprises, and finally constructing the integral evaluation system. A "five to one" structure has been proposed to enhance TCM injection effectiveness, safety and adaptability on the whole, which are from the following aspects： mechanism research, clinical evidence validation, literature information mining, sustainable development of resources and industrialization operation. Copyright© by the Chinese Pharmaceutical Association.

Prevalence of injections and knowledge of safe injections among rural residents in Central China.

PubMed

Yan, Y W; Yan, J; Zhang, G P; Gao, Z L; Jian, H X

2007-08-01

Abuse of the injection services, namely unnecessary injections and unsafe injections, exists extensively in developing countries. Unsafe injection practices contribute to the transmission of blood-borne pathogens. The aims of this study were to survey the prevalence of injections and knowledge of injection safety among the rural residents in Jingzhou district, Hubei, China and to provide scientific data for developing a health educational programme. A retrospective cross-sectional study was conducted in 12 villages, which were selected from the Jingzhou district by the random sampling method. 50 rural residents were interviewed per village using a questionnaire. Among the 595 residents studied, 192 had received at least one injection in the past three months, with an injection prevalence of 32.3 percent and an average of 0.93 injections. 90.3 percent of the rural residents knew that unsafe injections could transmit the following blood-borne pathogens: human immunodeficiency virus (74.4 percent), hepatitis B virus (55.8 percent) and hepatitis C virus (22.9 percent). Logistic regression analysis showed that the residents' age, educational level and residential area were important factors in influencing their knowledge about injection safety. The results indicated that the injection prevalence was high among rural residents in the study area, and their knowledge regarding injection safety should be further improved.

Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity.

PubMed

Castellanos, María Ana Martínez; Schwartz, Shulamit; García-Aguirre, Gerardo; Quiroz-Mercado, Hugo

2013-07-01

To evaluate ocular outcome in premature infants treated with intravitreal ranibizumab injections for retinopathy of prematurity (ROP) over a period of 3 years. An interventional case series. Premature infants with high-risk prethreshold or threshold ROP with plus disease received an off label monotherapy with intravitreal injections of ranibizumab. The primary outcome was treatment success defined as regression of neovascularisation (NV) and absence of recurrence. The secondary outcomes were ocular and systemic adverse events and visual acuity. Six eyes were included in the study and treated with intravitreal injections of ranibizumab. All showed complete resolution of NV after a single injection. The anti-angiogenic intravitreal injections allowed for continued normal vessel growth into the peripheral retina, without any signs of disease recurrence or progression during the follow up period. No ocular or systemic adverse effects were observed. Three years of follow up in a small series suggest that intravitreal ranibizumab injections for ROP result in apparently preserved ocular outcome. Further large scale studies are needed to address the long-term safety and efficacy.

Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.

PubMed

Carrade, Danielle D; Owens, Sean D; Galuppo, Larry D; Vidal, Martin A; Ferraro, Gregory L; Librach, Fred; Buerchler, Sabine; Friedman, Michael S; Walker, Naomi J; Borjesson, Dori L

2011-04-01

The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses. Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection. MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.

Knowledge, attitudes, beliefs, values, preferences, and feasibility in relation to the use of injection safety devices in healthcare settings: a systematic review.

PubMed

Tarabay, Rami; El Rassi, Rola; Dakik, Abeer; Harb, Alain; Ballout, Rami A; Diab, Batoul; Khamassi, Selma; Akl, Elie A

2016-07-13

Adopting technologies such as injection safety devices in healthcare settings can enhance injection safety. Developing guidelines for appropriate adoption of such technologies need to consider factors beyond evidence for their health effects. The objective of this study is to systematically review the published literature for evidence among healthcare workers and patients about knowledge, attitudes, beliefs, values, preferences, and feasibility in relation to the use of injection safety devices in healthcare settings. We included both qualitative and quantitative studies conducted with the general public, patients, and healthcare workers, administrators, or policy makers. We searched MEDLINE, EMBASE, CINHAL and CENTRAL. We used a duplicate and independent approach to title and abstract screening, full text screening, data abstraction and risk of bias assessment. Out of a total of 6568 identified citations, we judged fourteen studies as eligible for this systematic review. All these studies were surveys, conducted with healthcare workers in high-income countries. We did not identify any qualitative study, or a study of the general public, patients, healthcare administrators or policy makers. We did not identify any study assessing knowledge, or values assigned to outcomes relevant to injection safety devices. Each of the included studies suffered from methodological limitations, which lowers our confidence in their findings. Based on the findings of six studies, the injection safety devices were generally perceived as easy to use and as an improvement compared with conventional syringes. Some of these studies reported few technical problems while using the devices. In three studies assessing perceived safety, the majority of participants judged the devices as safe. Two studies reported positive perceptions of healthcare workers regarding patient tolerance of these injection safety devices. One study found that less than half the nurses felt comfortable using the insulin pens. Findings from four studies assessing preference and satisfaction were not consistent. This systematic review identified evidence that injection safety devices are generally perceived as easy to use, safe, and tolerated by patients. There were few reports of technical problems while using the devices and some discomfort by nurses using the insulin pens.

Devices for preventing percutaneous exposure injuries caused by needles in healthcare personnel.

PubMed

Reddy, Viraj K; Lavoie, Marie-Claude; Verbeek, Jos H; Pahwa, Manisha

2017-11-14

Percutaneous exposure injuries from devices used for blood collection or for injections expose healthcare workers to the risk of blood borne infections such as hepatitis B and C, and human immunodeficiency virus (HIV). Safety features such as shields or retractable needles can possibly contribute to the prevention of these injuries and it is important to evaluate their effectiveness. To determine the benefits and harms of safety medical devices aiming to prevent percutaneous exposure injuries caused by needles in healthcare personnel versus no intervention or alternative interventions. We searched CENTRAL, MEDLINE, EMBASE, NHSEED, Science Citation Index Expanded, CINAHL, Nioshtic, CISdoc and PsycINFO (until 11 November 2016). We included randomised controlled trials (RCT), controlled before and after studies (CBA) and interrupted time-series (ITS) designs of the effect of safety engineered medical devices on percutaneous exposure injuries in healthcare staff. Two of the authors independently assessed study eligibility and risk of bias and extracted data. We synthesized study results with a fixed-effect or random-effects model meta-analysis where appropriate. We included six RCTs with 1838 participants, two cluster-RCTs with 795 participants and 73,454 patient days, five CBAs with approximately 22,000 participants and eleven ITS with an average of 13.8 data points. These studies evaluated safe modifications of blood collection systems, intravenous (IV) systems, injection systems, multiple devices, sharps containers and legislation on the implementation of safe devices. We estimated the needlestick injury (NSI) rate in the control groups to be about one to five NSIs per 1000 person-years. There were only two studies from low- or middle-income countries. The risk of bias was high in 20 of 24 studies. Safe blood collection systems:We found one RCT that found a safety engineered blood gas syringe having no considerable effect on NSIs (Relative Risk (RR) 0.2, 95% Confidence Interval (95% CI) 0.01 to 4.14, 550 patients, very low quality evidence). In one ITS study, safe blood collection systems decreased NSIs immediately after the introduction (effect size (ES) -6.9, 95% CI -9.5 to -4.2) but there was no further decrease over time (ES -1.2, 95% CI -2.5 to 0.1, very low quality evidence). Another ITS study evaluated an outdated recapping shield, which we did not consider further. Safe Intravenous systemsThere was very low quality evidence in two ITS studies that NSIs were reduced with the introduction of safe IV devices, whereas one RCT and one CBA study provided very low quality evidence of no effect. However, there was moderate quality evidence produced by four other RCT studies that these devices increased the number of blood splashes when the safety system had to be engaged actively (relative risk (RR) 1.6, 95% CI 1.08 to 2.36). In contrast there was low quality evidence produced by two RCTs of passive systems that showed no effect on blood splashes. Yet another RCT produced low quality evidence that a different safe active IV system also decreased the incidence of blood leakages. Safe injection devicesThere was very low quality evidence provided by one RCT and one CBA study showing that introduction of safe injection devices did not considerably change the NSI rate. One ITS study produced low quality evidence showing that the introduction of safe passive injection systems had no effect on NSI rate when compared to safe active injection systems. Multiple safe devicesThere was very low quality evidence from one CBA study and two ITS studies. According to the CBA study, the introduction of multiple safe devices resulted in a decrease in NSI,whereas the two ITS studies found no change. Safety containersOne CBA study produced very low quality evidence showing that the introduction of safety containers decreased NSI. However, two ITS studies evaluating the same intervention found inconsistent results. LegislationThere was low to moderate quality evidence in two ITS studies that introduction of legislation on the use of safety-engineered devices reduced the rate of NSIs among healthcare workers. There was also low quality evidence which showed a decrease in the trend over time for NSI rates.Twenty out of 24 studies had a high risk of bias and the lack of evidence of a beneficial effect could be due to both confounding and bias. This does not mean that these devices are not effective. For safe blood collection systems, we found very low quality evidence of inconsistent effects on NSIs. For safe passive intravenous systems, we found very low quality evidence of a decrease in NSI and a reduction in the incidence of blood leakage events but moderate quality evidence that active systems may increase exposure to blood. For safe injection needles, the introduction of multiple safety devices or the introduction of sharps containers the evidence was inconsistent or there was no clear evidence of a benefit. There was low to moderate quality evidence that introduction of legislation probably reduces NSI rates.More high-quality cluster-randomised controlled studies that include cost-effectiveness measures are needed, especially in countries where both NSIs and blood-borne infections are highly prevalent.

Nanodrugs: pharmacokinetics and safety

PubMed Central

Onoue, Satomi; Yamada, Shizuo; Chan, Hak-Kim

2014-01-01

To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges. PMID:24591825

Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

PubMed

Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

2015-12-01

In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A simple 3-day "rush" venom immunotherapy protocol: documentation of safety.

PubMed

Kalogeromitros, D; Makris, M; Koti, I; Chliva, C; Mellios, A; Avgerinou, G; Theoharides, T C

2010-01-01

Venom immunotherapy (VIT) is the only effective treatment for hymenoptera hypersensitivity, but conventional protocols require a few weeks. We present the safety of a 3-day "rush" protocol that requires only 7 injections and 255 mgr cumulative dose before the 100 microg maintenance dose. Forty-nine patients (33 males, 16 females) of mean age 43.57+/-12.9 yrs received "rush" VIT. Only 7 injections were required until the maintenance dose of 100 mgr was reached on Day 5. On Day 1, four injections were administered with initial dose of 5 mgr and total dose of 75 microg. On Day 3 a cumulative dose of 180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients received Mixed Vespid preparation. Inclusion criteria were documented IgE-mediated allergy with intradermal sensitivity to < or =0.1 mgr/ml venom concentration and concomitant detection of specific venom IgE > or =0.35 kU/l. All patients reached the maintenance dose. Forty-nine patients received 65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%) were observed in 9 patients. The percentage of reactions/total injection number was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported documented field stings at least two months after VIT onset with only one reported mild systemic reaction. We propose a simple "rush" VIT protocol in an outpatient setting as an easy-to-perform alternative option for VIT induction phase. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Requirements for a transformerless power conditioning system

NASA Technical Reports Server (NTRS)

Klein, J.; Koerner, T.; Rippel, W.; Kalbach, J.

1984-01-01

Requirements for development of a Transformerless Power Conditioning Subsystem (TPCS) that will meet utility, manufacturer, and customer needs are detailed. Issues analyzed include current utility guidelines, safety and grounding issues that appear as local codes, various kinds of TPCS connections that can be developed, dc injection, and a brief survey of TPCS circuit topologies that will meet requirements. The major result is that a finite time exists for control operation before dc injection into the distribution transformer causes customer outage (on the order of seconds). This time permits the control system to sense a dc injection condition and remove the TPCS from the utility system. Requirements for such a control system are specified. A three wire connection will ensure balanced operation for customer loads and two wire connections caused average value dc to be injected into single phase loads. This type of connection also allows for the lowest array voltage. The conclusion is that requirements for a TPCS can be determined and that there are not showstopping issues preventing implementation. The actual design and topology of the TPCS was left for further study.

Automatic, sterile, and apyrogenic delivery of PET radiotracers from the cyclotron to the patient

NASA Astrophysics Data System (ADS)

Votaw, J. R.; Cashion, D. B.; Clanton, J. A.

1991-05-01

An automatic delivery remote injection system has been developed to administer either 13N-labelled ammonia, or 15O-labelled water or 18F-labelled FDG to patients. Automation increases the throughout and efficiency of the PET center, and remote dose administration ensures patient safety and reduces the radiation exposure to the technologist supervising the radiopharmaceutical injection. The remote dose administration apparatus utilizes a syringe pump to transfer liquid activity and a solenoid three-way valve to switch between lines connected to a patient and a receiving vial. To ensure apyrogenicity and sterility of the injected product, the entire system is washed with sterile water before it is used. Since the tracer is delivered in an ~ 8 ml bolus of water, the next delivery through the system is considered safe for injection if pyrogens are not detected at a threshold of 3 endotoxin units per ml (EU/ml) in the wash. Time delayed tests shows that the system may be left unused for up to 6 h before the wash must be repeated.

Methodological approaches to developing and establishing the body of evidence on post-marketing Chinese medicine safety.

PubMed

Liao, Xing; Robinson, Nicola

2013-07-01

Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, postmarketing surveillance (PMS) has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions (ADRs). Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detect ADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

PubMed

Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

2017-09-01

Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Reevaluation of the post-marketing safety of Shuxuening injection based on real-world and evidence-based evaluations.

PubMed

Wang, Can; Shi, Qing-Ping; Ding, Feng; Jiang, Xiao-Dong; Tang, Wei; Yu, Mei-Ling; Zhu, Jian-Hua

2018-01-01

To evaluate the factors influencing suspected hypersensitivity and adverse systemic reactions after Shuxuening injection and to provide innovative ideas and methods for the reevaluation of post-marketing safety of Shuxuening. This study used a prospective, nested case-control study design, combined with a prescription sequence analysis design method. It classified patients who exhibited trigger signals after administration of Shuxuening injection as suspected allergic patients and made comparisons with patients who did not report adverse effects to calculate the correlation between relevant risk factors and suspected allergic reactions. Randomized controlled studies and cohort studies of the adverse drug reaction (ADR) of Shuxuening were performed using a computer database. Data retrieval was carried out by the foundation governing the individual database. Meta-analysis was performed by using R3.2.3 software to evaluate the ADRs of Shuxuening. The results of real-world study showed that administration of Shuxuening in combination with potassium aspartate and magnesium, atorvastatin calcium, Shengmai injection, pantoprazole sodium, or high-dose medication was a risk factor for suspected allergic reactions. Meta-analysis showed that the incidence of adverse events was 5.84% (95% CI 0.0499; 0.0674), and serious adverse reaction rate was 4.36% (95% CI 0.0188; 0.0760) when Shuxuening was used in combination with these drugs. The incidence of allergic reaction was also influenced by the vehicle, duration of treatment, single dose, and indicated vs off-label use. Risk factors for adverse reaction following the use of Shuxuening injection in patients are associated with a single dose, vehicle, type of disease, and combination with potassium aspartate, atorvastatin calcium, Shengmai injection, injection with pantoprazole sodium, and other drugs. Physicians should be careful to follow guidelines when administering this drug. We further propose that the unique methodology used in this study may be useful for reevaluation of the safety of other traditional Chinese medicines.

Preclinical safety study of a recombinant Streptococcus pyogenes vaccine formulated with aluminum adjuvant.

PubMed

HogenEsch, Harm; Dunham, Anisa; Burlet, Elodie; Lu, Fangjia; Mosley, Yung-Yi C; Morefield, Garry

2017-02-01

A recombinant vaccine composed of a fusion protein formulated with aluminum hydroxide adjuvant is under development for protection against diseases caused by Streptococcus pyogenes. The safety and local reactogenicity of the vaccine was assessed by a comprehensive series of clinical, pathologic and immunologic tests in preclinical experiments. Outbred mice received three intramuscular injections of 1/5th of the human dose (0.1 ml) and rabbits received two injections of the full human dose. Control groups received adjuvant or protein antigen. The vaccine did not cause clinical evidence of systemic toxicity in mice or rabbits. There was a transient increase of peripheral blood neutrophils after the third vaccination of mice. In addition, the concentration of acute phase proteins serum amyloid A and haptoglobin was significantly increased 1 day after injection of the vaccine in mice. There was mild transient swelling and erythema of the injection site in both mice and rabbits. Treatment-related pathology was limited to inflammation at the injection site and accumulation of adjuvant-containing macrophages in the draining lymph nodes. In conclusion, the absence of clinical toxicity in two animal species suggest that the vaccine is safe for use in a phase I human clinical trial. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

PubMed

Miller, Elaine R; Lewis, Paige; Shimabukuro, Tom T; Su, John; Moro, Pedro; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2018-03-26

Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently reported to VAERS following ZVL. Overall, our results are reassuring regarding the safety of ZVL.

Injection safety among primary health care workers in Jazan Region, Saudi Arabia.

PubMed

Ismail, A A; Mahfouz, M S; Makeen, A

2014-07-01

Occupational exposure to percutaneous injuries is a substantial source of infections with blood-borne pathogens among health-care workers. Few studies evaluated injection safety practices in Saudi Arabia. To examine the structure and process of injection safety at primary health care level in Jazan health district, to evaluate knowledge, attitudes, and practices of primary health care physicians and nurses towards injection safety, and to determine the incidence of needle stick injuries among health care workers in Jazan region, Saudi Arabia. A cross-sectional study was conducted in Jazan primary health care centers (PHCCs), Saudi Arabia from September 2011 to March 2012. Data were collected using an observational checklist and data collection sheet. Jazan city health district was chosen at random from the 14 health sectors in Jazan region. All the 33 (10 urban, and 23 rural) PHCCs of Jazan city were included in this study to get the predetermined sample size of health care workers. 200 health care workers (HCWs) were recruited (29% physicians, and 71% nurses). Syringes in the PHCCs were disposable (100%), individually packed (92%), and available at all volumes (98%). Methods of safe disposal of needles and sharps were also operated through contracting with professional companies in 84.8% of instances. Urban PHCCs had more posts for injection safety promotion than rural centers (p=0.02). Continuous Medical Education (CME) programs on infection control were present in only 60% of PHCCs. At least 95% of HCWs in Jazan believed that sharp objects should be kept in a puncture-proof container, kept in a closed container, or disposed by a professional company. More than 80% of HCWs washed their hands by soap and water and cleaned them by alcohol before giving injection, and also got the three doses of hepatitis B vaccine.The rate of needle stick injury in the past year was 14%, without a significant difference between nurses and physicians (p=0.8). Jazan PHCCs have reasonable facilities that prevent needle-stick injuries. We need to design and implement more educational programs on safety injection, and increase promotion of safety injection posters, especially in rural PHCCs.

U.S. Space Station Freedom waste fluid disposal system with consideration of hydrazine waste gas injection thrusters

NASA Technical Reports Server (NTRS)

Winters, Brian A.

1990-01-01

The results are reported of a study of various methods for propulsively disposing of waste gases. The options considered include hydrazine waste gas injection, resistojets, and eutectic salt phase change heat beds. An overview is given of the waste gas disposal system and how hydrozine waste gas injector thruster is implemented within it. Thruster performance for various gases are given and comparisons with currently available thruster models are made. The impact of disposal on station propellant requirements and electrical power usage are addressed. Contamination effects, reliability and maintainability assessments, safety issues, and operational scenarios of the waste gas thruster and disposal system are considered.

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans.

PubMed

Nagy, Christa F; Leach, Timothy S; King, Alex; Guttendorf, Robert

2017-11-10

Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6-9 days, and terminal half-life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection-site abscesses or hypersensitivity reactions occurred; no subjects developed treatment-emergent antitherapeutic antibodies over the study period of 71 days. © 2017, The American College of Clinical Pharmacology.

75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Hyaluronate Sodium

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... safety warning for use of hyaluronate sodium injectable solution in horses. DATES: This rule is effective... human food safety warning on product labeling. The supplemental NADA is approved as of December 11, 2009...

Delivery system for molten salt oxidation of solid waste

DOEpatents

Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

2002-01-01

The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

In-Flight Validation of a Pilot Rating Scale for Evaluating Failure Transients in Electronic Flight Control Systems

NASA Technical Reports Server (NTRS)

Kalinowski, Kevin F.; Tucker, George E.; Moralez, Ernesto, III

2006-01-01

Engineering development and qualification of a Research Flight Control System (RFCS) for the Rotorcraft Aircrew Systems Concepts Airborne Laboratory (RASCAL) JUH-60A has motivated the development of a pilot rating scale for evaluating failure transients in fly-by-wire flight control systems. The RASCAL RFCS includes a highly-reliable, dual-channel Servo Control Unit (SCU) to command and monitor the performance of the fly-by-wire actuators and protect against the effects of erroneous commands from the flexible, but single-thread Flight Control Computer. During the design phase of the RFCS, two piloted simulations were conducted on the Ames Research Center Vertical Motion Simulator (VMS) to help define the required performance characteristics of the safety monitoring algorithms in the SCU. Simulated failures, including hard-over and slow-over commands, were injected into the command path, and the aircraft response and safety monitor performance were evaluated. A subjective Failure/Recovery Rating (F/RR) scale was developed as a means of quantifying the effects of the injected failures on the aircraft state and the degree of pilot effort required to safely recover the aircraft. A brief evaluation of the rating scale was also conducted on the Army/NASA CH-47B variable stability helicopter to confirm that the rating scale was likely to be equally applicable to in-flight evaluations. Following the initial research flight qualification of the RFCS in 2002, a flight test effort was begun to validate the performance of the safety monitors and to validate their design for the safe conduct of research flight testing. Simulated failures were injected into the SCU, and the F/RR scale was applied to assess the results. The results validate the performance of the monitors, and indicate that the Failure/Recovery Rating scale is a very useful tool for evaluating failure transients in fly-by-wire flight control systems.

Safety becomes danger: dilemmas of drug-use in public space.

PubMed

Dovey, K; Fitzgerald, J; Choi, Y

2001-12-01

This paper provides a socio-spatial analysis of injecting drug-use in public space. It focuses on one urban district in Melbourne, Australia, which has become strongly identified with heroin sale and use in public space. Selling activities are camouflaged within a diverse street life while injecting sites are dispersed through a broad diversity of laneways, car parks and toilets. These injecting zones occupy liminal places which slide between categories of private and public, and which mediate complex and paradoxical relations between safety and danger. Those who inject in public space are caught in a dilemma--needing both privacy and exposure in the event of an overdose, safety from police becomes danger from an overdose. This empirical work, based on interview and spatial analysis, is presented as a basis for theorizing the socio-spatial construction of heroin use and for assessing the prospects for safe injecting.

[Onyx embolization for treatment of dural arteriovenous fistula: comparison of long- distance versus routine injection method].

PubMed

He, Xiao-Yan; Zhang, Guo-Zhong; Li, Ming-Zhou; Wang, Gang; Liu, Dan; Qi, Song-Tao; Li, Wei-Guang; Feng, Wen-Feng

2016-03-01

To compare the efficacy, clinical characteristics, safety, injection time and radiation exposure of Onyx embolization using a long-distance injection method and routine injection method for management of dural arteriovenous fistula (DAVF). The clinical data were retrospectively analyzed in 59 patients with DAVF treated with Onyx embolization using long-distance injection method (28 patients) and routine injection method (31 patients). The efficacy, safety, injection time and radiation exposure during Onyx embolization were compared between the two injections methods. The average radiation dose exposure to the surgeon per procedure was significantly lower in the long-distance injection group than in the routine group. The injection time (P=0.53), injection volume (P=0.78), number of supply arteries (P=0.80), Cognard types (P=0.67), and effect of embolization (P=0.88) were all similar between the two groups. Endovaseular treatment of intracranial DAVF with Onyx embolization using the long-distance injection method is feasible, safe and effective and can reduce the radiation exposure to the surgeon.

Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review.

PubMed

Lanzetta, Paolo; Mitchell, Paul; Wolf, Sebastian; Veritti, Daniele

2013-12-01

Antivascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of wet age-related macular degeneration (wAMD). Recent research has focused on evaluating competing agents and alternative dosage regimens, providing evidence to help determine optimal treatment strategies. We therefore conducted a review of clinical research studies in wAMD published since 2008 that compared anti-VEGF dosing regimens and therapies; seven studies met our inclusion criteria. Data on baseline disease characteristics, disease outcomes, safety (ocular and systemic) and treatment burden (injection and visit frequencies) were extracted on patients treated with ranibizumab 0.5 mg, bevacizumab 1.25 mg or aflibercept 2.0 mg for up to 2 years. For ranibizumab and bevacizumab, visual and anatomical outcomes at 1 and 2 years were superior using scheduled monthly (or 4 weekly (q4w)) compared with as needed or scheduled quarterly dosing regimens. Treatment outcomes were generally better for both drugs when more aggressive retreatment criteria were used, which resulted in more frequent injections. Bevacizumab, however, was associated with a 30-35% elevated rate of serious systemic adverse events compared with ranibizumab, regardless of dosing interval; further study in larger patient populations will be required to determine the validity of this finding. Intravitreal aflibercept injection every 8 weeks was non-inferior to ranibizumab q4w on all visual and anatomical endpoints at week 52, had a similar safety profile and required five fewer anti-VEGF injections.

[Pharmacokinetics and safety of aripiprazole long-acting injection, following multiple deltoid administrations in schizophrenia patients in Japan].

PubMed

Ishigooka, Jun; Noda, Takamasa; Nishiyama, Kosuke; Tamaru, Noriko; Shima, Tomoko; Yamasaki, Yumiko; Tadori, Yoshihiro

2016-06-01

Aripiprazole once-monthly (AOM) was previously approved for treatment of schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle provides a more accessible injection site. The present study was conducted in Japanese schizophrenia patients as a 24-week, open-label trial that assessed the pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once every 4 weeks administered in the deltoid muscle. Patients treated with an oral atypical antipsychotic (other than aripiprazole) continued to receive their pre-study medication up to 14 days after the first AOM 400 injection. The completion rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady-state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean aripiprazole AUC(28d), C(max) and C(min) were 165 μg x h/ml, 331 ng/ml and 201 ng/ml, respectively, which were similar to previously published pharmacokinetic parameters after the fifth gluteal injection of AOM 400. The most common treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most TEAEs were classified as mild in intensity. In conclusion, the deltoid injection of AOM can be considered an alternative route of administration, as deltoid and gluteal injections are interchangeable in terms of aripiprazole plasma concentrations, with no additional safety issues.

Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

PubMed

Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

2014-01-01

Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

PubMed

Li, Huiling; Palamoor, Mallika; Jablonski, Monica M

2016-10-01

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

Development and validation of techniques for improving software dependability

NASA Technical Reports Server (NTRS)

Knight, John C.

1992-01-01

A collection of document abstracts are presented on the topic of improving software dependability through NASA grant NAG-1-1123. Specific topics include: modeling of error detection; software inspection; test cases; Magnetic Stereotaxis System safety specifications and fault trees; and injection of synthetic faults into software.

A comprehensive situation assessment of injection practices in primary health care hospitals in Bangladesh

PubMed Central

2011-01-01

Background Understanding injection practices is crucial for evidence-based development of intervention initiatives. This study explored the extent of injection use and injection safety practices in primary care hospitals in Bangladesh. Methods The study employed both quantitative and qualitative research methods. The methods used were - a retrospective audit of prescriptions (n = 4320), focus group discussions (six with 43 participants), in-depth interviews (n = 38) with a range service providers, and systematic observation of the activities of injection providers (n = 120), waste handlers (n = 48) and hospital facilities (n = 24). Quantitative and qualitative data were assessed with statistical and thematic analysis, respectively, and then combined. Results As many as 78% of our study sample (n = 4230) received an injection. The most commonly prescribed injections (n = 3354) including antibiotics (78.3%), IV fluids (38.6%), analgesics/pain killers (29.4%), vitamins (26.7%), and anti-histamines (18.5%). Further, 43.7% (n = 1145) of the prescribed antibiotics (n = 2626) were given to treat diarrhea and 42.3% (n = 600) of IV fluids (n = 1295) were used to manage general weakness conditions. Nearly one-third (29.8%; n = 36/120) of injection providers reported needle-stick injuries in the last 6 months with highest incidences in Rajshahi division followed by Dhaka division. Disposal of injection needles, syringes and other materials was not done properly in 83.5% (n = 20/24) of the facilities. Health providers' safety concerns were not addressed properly; only 23% (n = 28/120) of the health providers and 4.2% (n = 2/48) of the waste handlers were fully immunized against Hepatitis B virus. Moreover, 73% (n = 87/120) of the injection providers and 90% (n = 43/48) of the waste handlers were not trained in injection safety practices and infection prevention. Qualitative data further confirmed that both providers and patients preferred injections, believing that they provide quick relief. The doctors' perceived injection use as their prescribing norm that enabled them to prove their professional credibility and to remain popular in a competitive health care market. Additionally, persistent pressure from hospital administration to use up injections before their expiry dates also influenced doctors to prescribe injections regardless of actual indications. Conclusions As far as the patients and providers' safety is concerned, this study demonstrated a need for further research exploring the dynamics of injection use and safety in Bangladesh. In a context where a high level of injection use and unsafe practices were reported, immediate prevention initiatives need to be operated through continued intervention efforts and health providers' training in primary care hospitals in Bangladesh. PMID:21985397

New horizons in local anesthesia.

PubMed

Lackey, A D

1998-08-01

The computer-controlled local anesthesia system and the TEA system present 21st-century alternatives to the traditional syringe. The TEA system is a non-invasive form of anesthesia that blocks pain electronically, using the same cellular mechanism as local chemical anesthesia. Targeted electronic anesthesia provides pain control for restorative dental procedures without the use of needles or postoperative discomfort, numbness, and swelling. The computer-assisted system outperforms syringes for traditional injections. This new system generates a precisely controlled anesthetic flow rate that eliminates the need for the operator to use thumb pressure to administer the injection. The lightweight pen-grasp handle results in greater tactile feedback, precision, operator ease, and patient comfort. The greatest advantage may be in the new techniques that it makes available. With these techniques, a dentist can target the teeth to achieve profound pulpal anesthesia, often without the annoying side effects of facial numbness. With this new advanced system in the maxillary arch, the AMSA injection offers clinical advantages over traditional anesthesia techniques, according to Dr. Mark Friedman, whom I consulted with earlier this year. In the mandibular arch, a safe and predictable PDL injection technique may replace the need for an inferior alveolar block in numerous clinical situations. The use of these modified injection techniques can have a positive influence on patient safety, patient comfort, and office productivity. Both of these systems take the fear and anxiety out of dental injections. They offer exciting advanced technology for local pain control. Significantly, if patient stress and anxiety are reduced, the operator immediately benefits. New horizons in local anesthesia offer improved opportunities for patient comfort using computer-controlled local anesthetic systems and TEA.

High Pressure Coolant Injection (HPCI) System Risk-Based Inspection Guide for Browns Ferry Nuclear Power Station

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, S.; DiBiasio, A.; Gunther, W.

1993-09-01

The High Pressure Coolant Injection (HPCI) system has been examined from a risk perspective. A System Risk-Based Inspection Guide (S-RIG) has been developed as an aid to HPCI system inspections at the Browns Ferry Nuclear Power Plant, Units 1, 2 and 3. The role of. the HPCI system in mitigating accidents is discussed in this S-RIG, along with insights on identified risk-based failure modes which could prevent proper operation of the system. The S-RIG provides a review of industry-wide operating experience, including plant-specific illustrative examples to augment the PRA and operational considerations in identifying a catalogue of basic PRA failuremore » modes for the HPCI system. It is designed to be used as a reference for routine inspections, self-initiated safety system functional inspections (SSFIs), and the evaluation of risk significance of component failures at the nuclear power plant.« less

Top-Off Injection and Higher Currents at the Stanford Synchrotron Radiation Lightsource

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauer, Johannes M.; Liu, James C.; Prinz, Alyssa A.

2011-04-05

The Stanford Synchrotron Radiation Lightsource (SSRL) at the SLAC National Accelerator Laboratory is a 234 m circumference storage ring for 3 GeV electrons with its synchrotron radiation serving currently 13 beamlines with about 27 experimental stations. It operated for long time with 100 mA peak current provided by usually three injections per day. In July 2009, the maximum beam current was raised to 200 mA. Over the period from June 2009 to March 2010, Top-Off operation started at every beamline. Top-Off, i.e., the injection of electrons into the storage ring with injection stoppers open, is necessary for SSRL to reachmore » its design current of 500 mA. In the future, the maximal power of the injection current will also soon be raised from currently 1.5 W to 5 W. The Radiation Protection Department at SLAC worked with SSRL on the specifications for the safety systems for operation with Top-Off injection and higher beam currents.« less

Intra-arterial catheter system to repeatedly deliver mesenchymal stem cells in a rat renal failure model.

PubMed

Katsuoka, Yuichi; Ohta, Hiroki; Fujimoto, Eisuke; Izuhara, Luna; Yokote, Shinya; Kurihara, Sho; Yamanaka, Shuichiro; Tajiri, Susumu; Chikaraish, Tatsuya; Okano, Hirotaka J; Yokoo, Takashi

2016-04-01

Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure. First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days. Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days. Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells.

Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

PubMed

Hunziker, Manuela; Mohanan, Nochiparambil; Puri, Prem

2013-05-01

Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema.

PubMed

Daull, Philippe; Paterson, Christopher A; Kuppermann, Baruch D; Garrigue, Jean-Sébastien

2013-03-01

Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT) DXP emulsions in preclinical models. Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to basal levels and no evidence of cataract formation. IVT injections of DXP emulsions were well tolerated and shown to be efficacious for the sustained release of the drug, with the potential to control vascular leakage up to 9 months following a single IVT injection. These data suggest that IVT injections of DXP emulsions could be a safe and effective alternative IVT drug delivery vehicle for corticosteroid to treat back of the eye diseases complicated by macular edema.

EXPERIMENTAL AND ANALYTICAL STUDIES OF REFLECTRO CONTROL FOR THE ADVANCED ENGINEERING TEST REACTOR. PART A. EXPERIMENTAL STUDIES WITH THE REFLECTOR CONTROL SYSTEM MODEL. PART B. ANALYTICAL STUDIES OF REFLECTOR CONTROL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertelson, P.C.; Francis, T.L.

1959-10-21

Studies of reflector control for the Advanced Engineering Test Reactor were made. The performance of various parts of the reflector control system model such as the safety reflector and the water jet educator, boric acid injection, and demineralizer systems is discussed. The experimental methods and results obtained are discussed. Four reflector control schemes were studied. The schemes were a single-region and three-region reflector schemes two separate reflectors, and two connected reflectors. Calculations were made of shim and safety reflector worth for a variety of parameters. Safety reflector thickness was varied from 7.75 to 0 inches, with and without boron. Boricmore » acid concentration was varied from 100 to 2% of saturation in the shim reflectors. Neutron flux plots are presented (C.J.G.)« less

The Efficacy and Safety of HA IDF Plus (with Lidocaine) Versus HA IDF (Without Lidocaine) in Nasolabial Folds Injection: A Randomized, Multicenter, Double-Blind, Split-Face Study.

PubMed

Lee, Jong-Hun; Kim, Seok-Hwan; Park, Eun-Soo

2017-04-01

Injection-related pain of dermal fillers is a consistent and bothersome problem for patients undergoing soft tissue augmentation. Reducing the pain could improve overall patient satisfaction. The purpose of this study was to compare the pain relief, efficacy, and safety of HA IDF plus containing lidocaine with HA IDF without lidocaine during correction of nasolabial folds (NLFs). Sixty-two subjects were enrolled in a randomized, multicenter, double-blind, split-face study of HA IDF plus and HA IDF for NLF correction. For split-face study, HA IDF plus was injected to one side of NLF, and HA IDF was injected to the other side. The first evaluation variable was the injection site pain measured using a 100-mm visual analogue scale (VAS). The second evaluation variables included the global aesthetic improvement scale, wrinkle severity rating scale, and adverse events. Immediately after injection, 91.94% of subjects experienced at least 10 mm decrease in VAS scores at the side injected with HA IDF plus compared with HA IDF, and the rate of subjects is statistically significant. The two fillers were not significantly different in safety profile or wrinkle correction during the follow-up visit. HA IDF plus significantly reduced the injection-related pain during NLFs correction compared with HA IDF without altering clinical outcomes or safety. Both HA IDF plus and HA IDF were considerably tolerated and most adverse reactions were mild and transient. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Model-based safety analysis of human-robot interactions: the MIRAS walking assistance robot.

PubMed

Guiochet, Jérémie; Hoang, Quynh Anh Do; Kaaniche, Mohamed; Powell, David

2013-06-01

Robotic systems have to cope with various execution environments while guaranteeing safety, and in particular when they interact with humans during rehabilitation tasks. These systems are often critical since their failure can lead to human injury or even death. However, such systems are difficult to validate due to their high complexity and the fact that they operate within complex, variable and uncertain environments (including users), in which it is difficult to foresee all possible system behaviors. Because of the complexity of human-robot interactions, rigorous and systematic approaches are needed to assist the developers in the identification of significant threats and the implementation of efficient protection mechanisms, and in the elaboration of a sound argumentation to justify the level of safety that can be achieved by the system. For threat identification, we propose a method called HAZOP-UML based on a risk analysis technique adapted to system description models, focusing on human-robot interaction models. The output of this step is then injected in a structured safety argumentation using the GSN graphical notation. Those approaches have been successfully applied to the development of a walking assistant robot which is now in clinical validation.

Metastatic renal cell carcinoma: CT-guided immunotherapy as a technically feasible and safe approach to delivery of gene therapy for treatment.

PubMed

Suh, Robert D; Goldin, Jonathan G; Wallace, Amanda B; Sheehan, Ramon E; Heinze, Stefan B; Gitlitz, Barbara J; Figlin, Robert A

2004-05-01

To assess the technical feasibility and safety of weekly outpatient percutaneous computed tomographic (CT)-guided intratumoral injections of interleukin-2 (IL-2) plasmid DNA in a wide variety of superficial and deep tumor sites. Twenty-nine patients with metastatic renal cell carcinoma and a total of 30 lesions measuring 1.0 cm(2) or greater in accessible thoracic (n = 15) or abdominal (n = 15) locations underwent up to three cycles of six weekly intratumoral IL-2 plasmid DNA injections. CT was used to guide needle placement and injection. After injection cycle 1, patients whose tumors demonstrated stable (< or =25% increase and < or =50% decrease in product of lesion diameters) or decreased size (>50% decrease in product of lesion diameters) advanced to injection cycle 2. Patients whose lesions decreased in size by more than 50% over the course of injection cycle 2 were eligible to begin injection cycle 3. An acceptable safety and technical feasibility profile for this technique was deemed to be (a) a safety and feasibility profile similar to that of single-needle biopsy and (b) an absence of serious adverse events (as defined in Title 21 of the Code of Federal Regulations) and/or unacceptable toxicities (as graded according to the National Cancer Institute Common Toxicity Criteria). A total of 284 intratumoral injections were performed, with a mean of 9.8 injections (range, 6-18 injections) received by each patient. Technical success (needle placement and injection of gene therapy agent) was achieved in all cases. Complications were experienced after 42 (14.8%) of the 284 injections. The most common complication was pneumothorax (at 32 [28.6%] of 112 intrathoracic injections), for which only one patient required catheter drainage. Complications occurred randomly throughout injection cycles and did not appear to increase as patients received more injections (P =.532). No patient experienced serious adverse events or unacceptable toxicities. Percutaneous CT-guided intratumoral immunotherapy injections are technically feasible and can be safely performed.

Design process of the nanofluid injection mechanism in nuclear power plants

NASA Astrophysics Data System (ADS)

Kang, Myoung-Suk; Jee, Changhyun; Park, Sangjun; Bang, In Choel; Heo, Gyunyoung

2011-04-01

Nanofluids, which are engineered suspensions of nanoparticles in a solvent such as water, have been found to show enhanced coolant properties such as higher critical heat flux and surface wettability at modest concentrations, which is a useful characteristic in nuclear power plants (NPPs). This study attempted to provide an example of engineering applications in NPPs using nanofluid technology. From these motivations, the conceptual designs of the emergency core cooling systems (ECCSs) assisted by nanofluid injection mechanism were proposed after following a design framework to develop complex engineering systems. We focused on the analysis of functional requirements for integrating the conventional ECCSs and nanofluid injection mechanism without loss of performance and reliability. Three candidates of nanofluid-engineered ECCS proposed in previous researches were investigated by applying axiomatic design (AD) in the manner of reverse engineering and it enabled to identify the compatibility of functional requirements and potential design vulnerabilities. The methods to enhance such vulnerabilities were referred from TRIZ and concretized for the ECCS of the Korean nuclear power plant. The results show a method to decouple the ECCS designs with the installation of a separate nanofluids injection tank adjacent to the safety injection tanks such that a low pH environment for nanofluids can be maintained at atmospheric pressure which is favorable for their injection in passive manner.

Design process of the nanofluid injection mechanism in nuclear power plants

PubMed Central

2011-01-01

Nanofluids, which are engineered suspensions of nanoparticles in a solvent such as water, have been found to show enhanced coolant properties such as higher critical heat flux and surface wettability at modest concentrations, which is a useful characteristic in nuclear power plants (NPPs). This study attempted to provide an example of engineering applications in NPPs using nanofluid technology. From these motivations, the conceptual designs of the emergency core cooling systems (ECCSs) assisted by nanofluid injection mechanism were proposed after following a design framework to develop complex engineering systems. We focused on the analysis of functional requirements for integrating the conventional ECCSs and nanofluid injection mechanism without loss of performance and reliability. Three candidates of nanofluid-engineered ECCS proposed in previous researches were investigated by applying axiomatic design (AD) in the manner of reverse engineering and it enabled to identify the compatibility of functional requirements and potential design vulnerabilities. The methods to enhance such vulnerabilities were referred from TRIZ and concretized for the ECCS of the Korean nuclear power plant. The results show a method to decouple the ECCS designs with the installation of a separate nanofluids injection tank adjacent to the safety injection tanks such that a low pH environment for nanofluids can be maintained at atmospheric pressure which is favorable for their injection in passive manner. PMID:21711896

Design process of the nanofluid injection mechanism in nuclear power plants.

PubMed

Kang, Myoung-Suk; Jee, Changhyun; Park, Sangjun; Bang, In Choel; Heo, Gyunyoung

2011-04-27

Nanofluids, which are engineered suspensions of nanoparticles in a solvent such as water, have been found to show enhanced coolant properties such as higher critical heat flux and surface wettability at modest concentrations, which is a useful characteristic in nuclear power plants (NPPs). This study attempted to provide an example of engineering applications in NPPs using nanofluid technology. From these motivations, the conceptual designs of the emergency core cooling systems (ECCSs) assisted by nanofluid injection mechanism were proposed after following a design framework to develop complex engineering systems. We focused on the analysis of functional requirements for integrating the conventional ECCSs and nanofluid injection mechanism without loss of performance and reliability. Three candidates of nanofluid-engineered ECCS proposed in previous researches were investigated by applying axiomatic design (AD) in the manner of reverse engineering and it enabled to identify the compatibility of functional requirements and potential design vulnerabilities. The methods to enhance such vulnerabilities were referred from TRIZ and concretized for the ECCS of the Korean nuclear power plant. The results show a method to decouple the ECCS designs with the installation of a separate nanofluids injection tank adjacent to the safety injection tanks such that a low pH environment for nanofluids can be maintained at atmospheric pressure which is favorable for their injection in passive manner.

Clinical, economic, and humanistic burden of needlestick injuries in healthcare workers

PubMed Central

Cooke, Catherine E; Stephens, Jennifer M

2017-01-01

Introduction Needlestick injuries (NSIs) from a contaminated needle put healthcare workers (HCWs) at risk of becoming infected with a blood-borne virus and suffering serious short- and long-term medical consequences. Hypodermic injections using disposable syringes and needles are the most frequent cause of NSIs. Objective To perform a systematic literature review on NSI and active safety-engineered devices for hypodermic injection. Methods MEDLINE, EMBASE, and COCHRANE databases were searched for studies that evaluated the clinical, economic, or humanistic outcomes of NSI or active safety-engineered devices. Results NSIs have been reported by 14.9%–69.4% of HCWs with the wide range due to differences in countries, settings, and methodologies used to determine rates. Exposure to contaminated sharps is responsible for 37%–39% of the worldwide cases of hepatitis B and C infections in HCWs. HCWs may experience serious emotional effects and mental health disorders after a NSI, resulting in work loss and post-traumatic stress disorder. In 2015 International US$ (IntUS$), the average cost of a NSI was IntUS$747 (range IntUS$199–1,691). Hypodermic injections, the most frequent cause of NSI, are responsible for 32%–36% of NSIs. The use of safety devices that cover the needle-tip after hypodermic injection lowers the risk of NSI per HCW by 43.4%–100% compared to conventional devices. The economic value of converting to safety injective devices shows net savings, favorable budget impact, and overall cost-effectiveness. Conclusion The clinical, economic, and humanistic burden is substantial for HCWs who experience a NSI. Safety-engineered devices for hypodermic injection demonstrate value by reducing NSI risk, and the associated direct and indirect costs, psychological stress on HCWs, and occupational blood-borne viral infection risk. PMID:29033615

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

PubMed

Ye, Xiaoqin; Wei, Xu; Xie, Yanming; Zou, Yihuai; Zhao, Xingquan; Han, Jianhua; Wang, Xinzhi; Ma, Yunzhi; Bi, Qi; Xie, Qingfan; Zhao, Jianjun; Cao, Xiaolan; Chen, Hongxia; Wang, Shizhong; Yan, Rongmei; Han, Zucheng; Yi, Danhui; Wang, Yongyan

2011-10-01

To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

PubMed

Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

2015-01-01

The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

PubMed Central

Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

2014-01-01

Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

Transient analysis of ”2 inch Direct Vessel Injection line break” in SPES-2 facility by using TRACE code

NASA Astrophysics Data System (ADS)

D'Amico, S.; Lombardo, C.; Moscato, I.; Polidori, M.; Vella, G.

2015-11-01

In the past few decades a lot of theoretical and experimental researches have been done to understand the physical phenomena characterizing nuclear accidents. In particular, after the Three Miles Island accident, several reactors have been designed to handle successfully LOCA events. This paper presents a comparison between experimental and numerical results obtained for the “2 inch Direct Vessel Injection line break” in SPES-2. This facility is an integral test facility built in Piacenza at the SIET laboratories and simulating the primary circuit, the relevant parts of the secondary circuits and the passive safety systems typical of the AP600 nuclear power plant. The numerical analysis here presented was performed by using TRACE and CATHARE thermal-hydraulic codes with the purpose of evaluating their prediction capability. The main results show that the TRACE model well predicts the overall behaviour of the plant during the transient, in particular it is able to simulate the principal thermal-hydraulic phenomena related to all passive safety systems. The performance of the presented CATHARE noding has suggested some possible improvements of the model.

Inferior or double joint spaces injection versus superior joint space injection for temporomandibular disorders: a systematic review and meta-analysis.

PubMed

Li, Chunjie; Zhang, Yifan; Lv, Jun; Shi, Zongdao

2012-01-01

To compare the effect and safety of inferior or double temporomandibular joint spaces drug injection versus superior temporomandibular joint space injection in the treatment of temporomandibular disorders. MEDLINE (via Ovid, 1948 to March 2011), CENTRAL (Issue 1, 2011), Embase (1984 to March 2011), CBM (1978 to March 2011), and World Health Organization International Clinical Trials Registry Platform were searched electronically; relevant journals as well as references of included studies were hand-searched for randomized controlled trials comparing effect or safety of inferior or double joint spaces drug injection technique with those of superior space injection technique. Risk of bias assessment with the tool recommended by Cochrane Collaboration, reporting quality assessment with CONSORT and data extraction, were carried out independently by 2 reviewers. Meta-analysis was delivered with RevMan 5.0.23. Four trials with 349 participants were included. All the included studies had moderate risk of bias. Meta-analysis showed that inferior or double spaces injection technique could significantly increase 2.88 mm more maximal mouth opening (P = .0001) and alleviate pain intensity in the temporomandibular area on average by 9.01 mm visual analog scale scores (P = .0001) compared with superior space injection technique, but could not markedly change synthesized clinical index (P = .05) in the short term; nevertheless, they showed more beneficial maximal mouth opening (P = .002), pain relief (P < .0001), and synthesized clinical variable (P < .0001) in the long term than superior space injection. No serious adverse events were reported. Inferior or double temporomandibular joint spaces drug injection technique shows better effect than superior space injection technique, and their safety is affirmative. However, more high-quality studies are still needed to test and verify the evidence. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Rapid and non-destructive identification of water-injected beef samples using multispectral imaging analysis.

PubMed

Liu, Jinxia; Cao, Yue; Wang, Qiu; Pan, Wenjuan; Ma, Fei; Liu, Changhong; Chen, Wei; Yang, Jianbo; Zheng, Lei

2016-01-01

Water-injected beef has aroused public concern as a major food-safety issue in meat products. In the study, the potential of multispectral imaging analysis in the visible and near-infrared (405-970 nm) regions was evaluated for identifying water-injected beef. A multispectral vision system was used to acquire images of beef injected with up to 21% content of water, and partial least squares regression (PLSR) algorithm was employed to establish prediction model, leading to quantitative estimations of actual water increase with a correlation coefficient (r) of 0.923. Subsequently, an optimized model was achieved by integrating spectral data with feature information extracted from ordinary RGB data, yielding better predictions (r = 0.946). Moreover, the prediction equation was transferred to each pixel within the images for visualizing the distribution of actual water increase. These results demonstrate the capability of multispectral imaging technology as a rapid and non-destructive tool for the identification of water-injected beef. Copyright © 2015 Elsevier Ltd. All rights reserved.

Percutaneous Direct Needle Puncture and Transcatheter N-butyl Cyanoacrylate Injection Techniques for the Embolization of Pseudoaneurysms and Aneurysms of Arteries Supplying the Hepato-pancreato-biliary System and Gastrointestinal Tract

PubMed Central

Yadav, Rajanikant R; Boruah, Deb K; Bhattacharyya, Vishwaroop; Prasad, Raghunandan; Kumar, Sheo; Saraswat, V A; Kapoor, V K; Saxena, Rajan

2016-01-01

Aims: The aim of this study was to evaluate the safety and clinical efficacy of percutaneous direct needle puncture and transcatheter N-butyl cyanoacrylate (NBCA) injection techniques for the embolization of pseudoaneurysms and aneurysms of arteries supplying the hepato-pancreato-biliary (HPB) system and gastrointestinal (GI) tract. Subjects and Methods: A hospital-based cross-sectional retrospective study was conducted, where the study group comprised 11 patients with pseudoaneurysms/aneurysms of arteries supplying the HPB system and GI tract presenting to a tertiary care center from January 2015 to June 2016. Four patients (36.4%) underwent percutaneous direct needle puncture of pseudoaneurysms with NBCA injection, 3 patients (27.3%) underwent transcatheter embolization with NBCA as sole embolic agent, and in 4 patients (36.4%), transcatheter NBCA injection was done along with coil embolization. Results: This retrospective study comprised 11 patients (8 males and 3 females) with mean age of 35.8 years ± 1.6 (standard deviation [SD]). The mean volume of NBCA: ethiodized oil (lipiodol) mixture injected by percutaneous direct needle puncture was 0.62 ml ± 0.25 (SD) (range = 0.5–1 ml), and by transcatheter injection, it was 0.62 ml ± 0.37 (SD) (range = 0.3–1.4 ml). Embolization with NBCA was technically and clinically successful in all patients (100%). No recurrence of bleeding or recurrence of pseudoaneurysm/aneurysm was noted in our study. Conclusions: Percutaneous direct needle puncture of visceral artery pseudoaneurysms and NBCA glue injection and transcatheter NBCA injection for embolization of visceral artery pseudoaneurysms and aneurysms are cost-effective techniques that can be used when coil embolization is not feasible or has failed. PMID:28123838

Epidural steroid injections: update on efficacy, safety, and newer medications for injection.

PubMed

Kozlov, N; Benzon, H T; Malik, K

2015-08-01

The best evidence for epidural injection appears to be in the setting of radicular pain with epidural steroid and non-steroid injections more efficacious than non-epidural injections. Studies showed the efficacy of non-particulate steroid to approach the efficacy of particulate steroid and very limited comparisons demonstrated no significant difference between epidural steroid and epidural non-steroid (local anesthetic) injection. Preliminary studies evaluating epidural injection of disease modifying anti-rheumatic drugs such etanercept and tocilizumab showed conflicting results and had significant limitations. Randomized studies support better efficacy of transforaminal injection due to greater incidence of ventral epidural spread of injectate when compared to interlaminar injection. Thus, the transforaminal approach is recommended when unilateral radicular pain is limited to one nerve root. However, the transforaminal approach is associated with greater incidence of central nervous system injury, including paraplegia, attributed to embolization of the particulate steroid. Recent studies showed that non-particulate steroids potentially last as long as particulate steroids. Therefore non-particulate steroid should be used in initial transforaminal epidural injection. Future studies should look into the role of adjunct diagnostic aids, including digital subtraction angiography, in detecting intravascular injection and the ideal site of needle placement, whether it is the safe triangle or the triangle of Kambin. Finally, the role of epidural disease -modifying antirheumatic drugs in the management of back pain needs to be better elucidated.

[Rapid screening and quality evaluation for the harmful substance 5-hydroxymethyl furfural in commercially available traditional Chinese medicine injection using LC-MS/MS method].

PubMed

Zang, Qing-ce; He, Jing-jing; Bai, Jin-fa; Zheng, Ya-jie; Zhang, Rui-ping; Li, Tie-gang; Wang, Zhong-hua; He, Jiu-ming; Abliz, Zeper

2013-11-01

To screen the harmful substance 5-hydroxymethyl furfural content in commercially available traditional Chinese medicine injection which are commonly used, and to preliminarily evaluate the quality of these injections, 5-hydroxymethyl furfural was taken as an index. The contents of 5-hydroxymethyl furfural in 56 samples which consist of 23 kinds of traditional Chinese medicine injections and glucose injection were determined using LC-MS/MS, and 5-hydroxymethyl furfural was detected in 52 of these samples. The minimal content was 0.0038 microg x L(-1) and the maximum content was 1420 microg x mL(-1). The contents of 5-hydroxymethyl furfural were significantly different in traditional Chinese medicine injection which came from different kinds, manufacturers or batches. The results showed the quality difference of commercially available traditional Chinese medicine injection is significant taking 5-hydroxymethyl furfural content as assessment index. More attention should be paid to the safety of 5-hydroxymethyl furfural in traditional Chinese medicine injection, and unified limitation standard should be set to improve medication safety of traditional Chinese medicine injection.

1985 Particle Accelerator Conference: Accelerator Engineering and Technology, 11th, Vancouver, Canada, May 13-16, 1985, Proceedings

NASA Astrophysics Data System (ADS)

Strathdee, A.

1985-10-01

The topics discussed are related to high-energy accelerators and colliders, particle sources and electrostatic accelerators, controls, instrumentation and feedback, beam dynamics, low- and intermediate-energy circular accelerators and rings, RF and other acceleration systems, beam injection, extraction and transport, operations and safety, linear accelerators, applications of accelerators, radiation sources, superconducting supercolliders, new acceleration techniques, superconducting components, cryogenics, and vacuum. Accelerator and storage ring control systems are considered along with linear and nonlinear orbit theory, transverse and longitudinal instabilities and cures, beam cooling, injection and extraction orbit theory, high current dynamics, general beam dynamics, and medical and radioisotope applications. Attention is given to superconducting RF structures, magnet technology, superconducting magnets, and physics opportunities with relativistic heavy ion accelerators.

Subcutaneous injections: preventing needlestick injuries in the community.

PubMed

Aziz, Ann-Marie

2012-06-01

Community nurses provide care to patients in a variety of settings, for example health centres, community hospitals, patients' homes, residential and nursing homes. Administering subcutaneous injections to patients in the community is an everyday activity for many nurses in clinical practice. Many problems related to being 'sharps safe' are common to both community nurses and hospital staff. The majority of subcutaneous injections administered in the community are for patients with diabetes. Reducing needlestick injuries after the administration of subcutaneous injections in the community remains paramount to all NHS staff. This article provides information on what national standards to employ when administrating subcutaneous injections and what safety practices should be undertaken for good sharps management. Staff administering subcutaneous injections in the community need to ensure that they are updated on the latest developments in safety needle devices in order to prevent needlestick injuries and provide safe, effective and individualised care for their patients.

Assessment of injection practice in primary health care facilities of Shiraz, Iran.

PubMed

Mclaws, Mary-Louise; Ghahramani, Sulmaz; Palenik, Charles John; Keshtkar, Vahid; Askarian, Mehrdad

2014-03-01

Occupational risk for several bloodborne viruses is attributable to unsafe injection practices. To understand injection frequency and safety, we surveyed injection rates and factors influencing injection prescription in primary health care facilities and associated health clinics in Shiraz, Iran. We used both quantitative and qualitative approaches to study the frequency and safety of injections delivered in 27 primary health care facilities. We used observations and 3 data collecting tools. Patterns of 600 general practice physicians' (GPs) prescriptions were also reviewed. In-depth interviews to elicit the factors contributing to injection prescriptions were conducted. The annual per capita injection rate was 3.12. Corticosteroids were prescribed more frequently than antibiotics (P < .001). Knowledge of participants concerning transmission risks for 3 of the most common bloodborne infections (BBIs) was less than 75%. Factors affecting use of injections by GPs included strong patient preference for injections over oral medications and financial benefit for GPs, especially those in private practice settings. Frequency of therapeutic injections in the participating facilities in Shiraz was high. Sociocultural factors in the patient community and their beliefs in the effectiveness of injections exerted influence on GP prescribing practices. Programs for appropriate and safe injection practices should target GP and injection providers, as well as patients, informing them about alternative treatments and possible complications of unnecessary and unsafe injections. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies.

PubMed

Witthaut, Jörg; Jones, Graeme; Skrepnik, Nebojsa; Kushner, Harvey; Houston, Anthony; Lindau, Tommy R

2013-01-01

The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20° to 100°) or proximal interphalangeal (PIP) joints (20° to 80°) could receive up to three 0.58-mg CCH injections per cord (up to 5 total injections per patient). We performed standardized finger extension procedures to disrupt injected cords the next day, with follow-up 1, 2, 6, and 9 months thereafter. The primary end point (clinical success) was reduction in contracture to within 0° to 5° of full extension 30 days after the last injection. Clinical improvement was defined as 50% or more reduction from baseline contracture. Dupuytren cords affecting 879 joints (531 MCP and 348 PIP) in 587 patients were administered CCH injections at 14 U.S. and 20 Australian/European sites, with similar outcomes in both studies. Clinical success was achieved in 497 (57%) of treated joints using 1.2 ± 0.5 (mean ± SD) CCH injections per cord. More MCP than PIP joints achieved clinical success (70% and 37%, respectively) or clinical improvement (89% and 58%, respectively). Less severely contracted joints responded better than those more severely contracted. Mean change in contracture was 55° for MCP joints and 25° for PIP joints. With average contracture reductions of 73% and improvements in range of motion by 30°, most patients (92%) were "very satisfied" (71%) or "quite satisfied" (21%) with treatment. Physicians rated change from baseline as "very much improved" (47%) or "much improved" (35%). The CCH injections were well tolerated, causing no tendon ruptures or systemic reactions. Collagenase clostridium histolyticum was an effective, minimally invasive option for the treatment of Dupuytren contracture of a broad range of severities. Most treated joints (625 of 879) required a single injection. Treatment earlier in the course of disease provided improved outcomes. Therapeutic IV. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Simulation and Measurement of Through-the-Earth, Extremely Low-Frequency Signals Using Copper-Clad Steel Ground Rods.

PubMed

Damiano, Nicholas William; Yan, Lincan; Whisner, Bruce; Zhou, Chenming

2017-01-01

The underground mining environment can greatly affect radio signal propagation. Understanding how the earth affects signal propagation is a key to evaluating communications systems used during a mine emergency. One type of communication system is through-the-earth, which can utilize extremely low frequencies (ELF). This paper presents the simulation and measurement results of recent National Institute for Occupational Safety and Health (NIOSH) research aimed at investigating current injection at ELF, and in particular, ground contact impedance. Measurements were taken at an outside surface testing location. The results obtained from modeling and measurement are characterized by electrode impedance, and the voltage received between two distant electrodes. This paper concludes with a discussion of design considerations found to affect low-frequency communication systems utilizing ground rods to inject a current into the earth.

Simulation and Measurement of Through-the-Earth, Extremely Low-Frequency Signals Using Copper-Clad Steel Ground Rods

PubMed Central

Damiano, Nicholas William; Yan, Lincan; Whisner, Bruce; Zhou, Chenming

2017-01-01

The underground mining environment can greatly affect radio signal propagation. Understanding how the earth affects signal propagation is a key to evaluating communications systems used during a mine emergency. One type of communication system is through-the-earth, which can utilize extremely low frequencies (ELF). This paper presents the simulation and measurement results of recent National Institute for Occupational Safety and Health (NIOSH) research aimed at investigating current injection at ELF, and in particular, ground contact impedance. Measurements were taken at an outside surface testing location. The results obtained from modeling and measurement are characterized by electrode impedance, and the voltage received between two distant electrodes. This paper concludes with a discussion of design considerations found to affect low-frequency communication systems utilizing ground rods to inject a current into the earth. PMID:29176916

Epidural Steroid Injections are Safe and Effective: Multisociety Letter in Support of the Safety and Effectiveness of Epidural Steroid Injections.

PubMed

Kennedy, David J; Levin, Joshua; Rosenquist, Richard; Singh, Virtaj; Smith, Clark; Stojanovic, Milan P; Vorobeychik, Yakov

2015-05-01

In April 2014, the Food and Drug Administration (FDA) issued a Drug Safety Communication requesting that corticosteroid labeling include warnings that injection of corticosteroids into the epidural space of the spine may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death. The International Spine Intervention Society spearheaded a collaboration of more than a dozen other medical societies in submitting the letter below to the FDA on November 7, 2014. We are publishing the letter to ensure that the readership of Pain Medicine is aware of the multisociety support for the safety and effectiveness of these procedures. A special note of thanks to all of the societies who signed on in support of the message. Wiley Periodicals, Inc.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

PubMed

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.

Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

PubMed Central

Tan, James-Kevin Y.; Sellers, Drew L.; Pham, Binhan; Pun, Suzie H.; Horner, Philip J.

2016-01-01

With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application. PMID:27847462

Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

PubMed

Ha, Chul-Won; Park, Yong-Beom; Choi, Chong-Hyuk; Kyung, Hee-Soo; Lee, Ju-Hong; Yoo, Jae Doo; Yoo, Ju-Hyung; Choi, Choong-Hyeok; Kim, Chang-Wan; Kim, Hee-Chun; Oh, Kwang-Jun; Bin, Seong-Il; Lee, Myung Chul

2017-05-26

This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

PubMed

Invernizzi, M; Carda, S; Molinari, C; Stagno, D; Cisari, C; Baricich, A

2015-08-01

The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. Case control study. Eleven stroke survivors with spastic hemiplegia. Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. None of the variable considered showed statistically significant changes after BoNT-A injection. The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate.

PubMed

Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

2012-01-01

The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

A global health partnership's use of time-limited support to catalyze health practice change: the case of GAVI's Injection Safety Support.

PubMed

Levin, Ann; Fang, Arnold; Hansen, Peter M; Pyle, David; Dia, Ousmane; Schwalbe, Nina

2010-09-27

This paper presents the findings of a study to assess the effectiveness and sustainability of a GAVI (Global Alliance of Vaccines and Immunization) sponsored, time-limited Injection Safety (INS) support. The support came in two forms: 1) in-kind, in the form of AD syringes and safety boxes, and 2) in cash, for those countries that already had a secure, multi-year source of AD syringes and safety boxes, but proposed to use INS support to strengthen their injection safety activities. In total, GAVI gave INS support for a three-year period to 58 countries: 46 with commodities and 12 with cash support. To identify variables that might be associated with financial sustainability, frequencies and cross-tabulations were run against various programmatic and socio-economic variables in the 58 countries. All but two of the 46 commodity-recipient countries were able to replace and sustain the use of AD syringes and safety boxes after the end of their GAVI INS support despite the fact that standard disposable syringes are less costly than ADs (10-15 percent differential). In addition, all 12 cash-recipient countries continued to use AD syringes and safety boxes in their immunization programs in the years following GAVI INS assistance. At the same time, countries were often not prepared for the increased waste management requirements associated with the use of the syringes, suggesting the importance of anticipating challenges with the introduction of new technologies. The sustained use of AD syringes in countries receiving injection safety support from GAVI, in a majority of cases through government financing, following the completion of three years of time-limited support, represents an early indication of how GHPs can contribute to improved health outcomes in immunization safety in the world's poorest countries in a sustainable way.

A protocol for the retina surgeon's safe initial intravitreal injections.

PubMed

Frenkel, Ronald E P; Haji, Shamim A; La, Melvin; Frenkel, Max P C; Reyes, Angela

2010-11-10

To determine the safety of a surgeon's initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure. A retrospective chart review. Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections. The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone-iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection. Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage. There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections. The incidence of serious complications was very low for the intravitreal injections given. A surgeon's initial intravitreal injections may be performed with a very high degree of safety using this protocol.

Are nursing students safe when choosing gluteal intramuscular injection locations?

PubMed

Cornwall, J

2011-01-01

Nurses are required to perform gluteal intramuscular (IM) injections in practice. There are dangers associated with erroneous performance of this task, particularly with dorsogluteal injections. Knowledge regarding safe injection practice is therefore vital for nursing students. Fifty-eight second year students at a New Zealand Nursing School were given schematic drawings of the posterior and lateral aspects of the gluteal region. They were asked to mark and justify the safest location for gluteal IM injections. Fifty-seven students marked the dorsal schematic and one the lateral, with 38 (66.7%) marking in the upper outer quadrant (UOQ). Twenty indicating the UOQ (52.6%) wrote 'sciatic' or 'nerve' in justifying their location. Nineteen (33.3%) marked a location outside the UOQ; nine (47.4%) of these mentioned 'sciatic' or 'nerve' as reasons for injection safety. Overall, 50% of students mentioned 'sciatic' or 'nerve' in justifying the safety of their chosen injection location. Results suggest some second year nursing students do not understand safe gluteal IM injection locations and rationale. Current teaching practices and IM injection techniques could be revisited to prepare students more effectively; this may help prevent pathologies arising from this procedure.

Vibration Anesthesia for Pain Reduction During Intralesional Steroid Injection for Keloid Treatment.

PubMed

Park, Kui Young; Lee, Yohan; Hong, Ji Yeon; Chung, Won Soon; Kim, Myeung Nam; Kim, Beom Joon

2017-05-01

Patients suffer significant pain during intralesional steroid injection treatment for keloids and hypertrophic scars. Vibration anesthesia has been shown to effectively and safely alleviate pain sensations, likely by reducing pain transmission from peripheral receptors to the brain. The objective was to evaluate the efficacy, safety, and patient satisfaction associated with vibration anesthesia for reducing pain during intralesional corticosteroid injection. The authors recruited 40 patients with 58 keloids who were scheduled to undergo intralesional triamcinolone acetonide (TA) injections. Half of each keloid was injected with concomitant vibration anesthesia, whereas the other half was injected without vibration anesthesia. Pain experienced by patients during both procedures was assessed according to visual analog scale (VAS) score. The authors also assessed procedure safety. The mean VAS score during intralesional TA injection therapy without vibration was 5.88 ± 2.34. By contrast, the same patients yielded a mean VAS score during intralesional TA injection therapy with vibration of 3.28 ± 1.85; the difference between the mean scores was significant (p < .05). Thirty-nine (97.5%) patients tolerated this therapy well. Vibration anesthesia is a promising option for reducing pain during keloid treatment with intralesional steroid injection.

Efficacy and safety of flurbiprofen axetil in the prevention of pain on propofol injection: a systematic review and meta-analysis.

PubMed

Zhang, Lieliang; Zhu, Juan; Xu, Lei; Zhang, Xunlei; Wang, Hongyu; Luo, Zhonghua; Zhao, Yamei; Yu, Yi; Zhang, Yong; Shi, Hongwei; Bao, Hongguang

2014-06-17

Pain on injection is an acknowledged adverse effect (AE) of propofol administration for the induction of general anesthesia. Flurbiprofen axetil has been reported to reduce the pain of injection. However, results of published papers on the efficacy of flurbiprofen axetil in managing pain on injection of propofol are inconsistent. We conducted a comprehensive meta-analysis of studies to appraise the efficacy and safety of flurbiprofen axetil for controlling pain induced by propofol injection. The pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) was calculated employing fixed- or random-effects models, depending upon the heterogeneity of the included trials. Compared with the placebo group, flurbiprofen axetil allows more patients to have no pain (RR 3.51, 95% CI 2.22-5.55, p=0.000), and decreases the cumulative number of patients with mild, moderate, and severe pain on injecting propofol (RR 0.70, 95% CI 0.58-0.86, p=0.000; RR 0.59, 95% CI 0.46-0.75, p=0.000; RR 0.25, 95% CI 0.16-0.38, p=0.000, respectively). In the stratified analysis by the doses, flurbiprofen axetil at a dose of over 50 mg was found to be effective in reducing propofol-induced pain on injection; however, there were no significant differences in relieving pain between treatment and placebo groups with flurbiprofen axetil at a dose of 25 mg. In terms of drug safety, there were no adverse effects (AEs) reported between flurbiprofen axetil-based regimens and placebo regimens. Flurbiprofen axetil, an injectable prodrug of flurbiprofen, can significantly prevent or relieve the pain induced by propofol injection. More studies are required to assess its adverse effects.

Preliminary LOCA analysis of the westinghouse small modular reactor using the WCOBRA/TRAC-TF2 thermal-hydraulics code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, J.; Kucukboyaci, V. N.; Nguyen, L.

2012-07-01

The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using themore » WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)« less

Towards safe injection practices for prevention of hepatitis C transmission in South Asia: Challenges and progress.

PubMed

Janjua, Naveed Zafar; Butt, Zahid Ahmad; Mahmood, Bushra; Altaf, Arshad

2016-07-07

To summarize the available information about injection use and its determinants in the South Asian region. We searched published and unpublished literature on injection safety in South Asia published during 1995-2016 using the keywords "injection" "unsafe injection" and "immunization injection" and combined these with each of the countries and/or their respective states or provinces in South Asia. We used a standardized questionnaire to abstract the following data from the articles: the annual number of injections per capita, the proportion of injections administered with a reused syringe or needle, the distribution of injections with respect to prescribers and providers and determinants of injection use. Although information is very limited for certain countries (i.e., Bhutan, Maldives and Sri Lanka), healthcare injection use is very common across South Asia, with cross-country rates ranging from 2.4 to 13.6 injections/person/year. Furthermore, recent studies show that 5% to 50% of these injections are provided with reused syringes, thus creating potential to transmission of blood-borne pathogens. Qualified and unqualified practitioners, especially in the private sector, are the major drivers behind injection use, but patients also prefer injections, especially among the rural, poor or uneducated in certain countries. According to available data, Pakistan and India have recently taken steps towards achieving safe injection. Potential interventions include the introduction of reuse prevention devices, and patient-, community- and patient/community and provider-centered interventions to change population and practitioner behavior. Injection use is common in South Asian countries. Multilevel interventions aiming at patients, providers and the healthcare system are needed to reduce injection use and reuse.

Intrathecal Spread of Injectate Following an Ultrasound-Guided Selective C5 Nerve Root Injection in a Human Cadaver Model.

PubMed

Falyar, Christian R; Abercrombie, Caroline; Becker, Robert; Biddle, Chuck

2016-04-01

Ultrasound-guided selective C5 nerve root blocks have been described in several case reports as a safe and effective means to anesthetize the distal clavicle while maintaining innervation of the upper extremity and preserving diaphragmatic function. In this study, cadavers were injected with 5 mL of 0.5% methylene blue dye under ultrasound guidance to investigate possible proximal and distal spread of injectate along the brachial plexus, if any. Following the injections, the specimens were dissected and examined to determine the distribution of dye and the structures affected. One injection revealed dye extended proximally into the epidural space, which penetrated the dura mater and was present on the spinal cord and brainstem. Dye was noted distally to the divisions in 3 injections. The anterior scalene muscle and phrenic nerve were stained in all 4 injections. It appears unlikely that local anesthetic spread is limited to the nerve root following an ultrasound-guided selective C5 nerve root injection. Under certain conditions, intrathecal spread also appears possible, which has major patient safety implications. Additional safety measures, such as injection pressure monitoring, should be incorporated into this block, or approaches that are more distal should be considered for the acute pain management of distal clavicle fractures.

Fukushima Daiichi Nuclear Accident; based on the Final Report of Atomic Energy Society of Japan

NASA Astrophysics Data System (ADS)

Sekimura, Naoto

2014-09-01

The Atomic Energy Society of Japan (AESJ) published the Final Report of the AESJ Investigation Committee on Fukushima Daiichi NPS Accident in March 2014. The AESJ is responsible to identify the underlying root causes of the accident through technical surveys and analyses, and to offer solutions for nuclear safety. At the Fukushima Daiichi, Units 1 to 3, which were under operation, were automatically shut down at 14:46 on March 11, 2011 by the Tohoku District-off the Pacific Ocean Earthquake. About 50 minutes later, the tsunami flooded and destroyed the emergency diesel generators, the seawater cooling pumps, the electric wiring system and the DC power for Units 1, 2 and 4, resulting in loss of all power except for an air-cooled emergency diesel generator at Unit 6. Unit 3 lost all AC power, and later lost DC before dawn of March 13. Cooling the reactors and monitoring the results were heavily dependent on electricity for high-pressure water injection, depressurizing the reactor, low pressure water injection, and following continuous cooling. In Unit 3, for example, recent re-evaluation in August 2014 by TEPCO shows that no cooling water was injected into the reactor core region after 8 PM on March 12, leading to the fuel melting from 5:30 AM on March 13. Even though seawater was injected from fire engines afterwards, the rupture of pressure vessel was caused and the majority of melted fuel dropped into the containment vessel of Unit 3. The estimation of amount of radioactive materials such as Xe-133, I-131, Cs-137 and Cs-134, emitted to the environment from Units 1 to 3 is discussed in the presentation. Direct causes of the accident identified in the AESJ Report were, 1) inadequate tsunami measures, 2) inadequate severe accident management measures and 3) inadequate emergency response, post-accident management/mitigation, and recovery measures. These were caused by the following underlying factors, i.e., a) lack of awareness on the roles and responsibilities by experts, b) shortfalls in establishing safety measures and fostering safety awareness by utilities, c) lack of safety awareness by the regulatory body, d) inadequacies in attitude of learning from efforts and collaborations in the international community, and e) shortage of qualified personnel to ensure safety and inadequacies in organization and management framework.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

PubMed

Guarnieri, M; Brayton, C; Sarabia-Estrada, R; Tyler, B; McKnight, P; DeTolla, L

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

PubMed Central

Brayton, C.; Sarabia-Estrada, R.; McKnight, P.; DeTolla, L.

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy. PMID:28492060

Patient Safety Threat - Syringe Reuse

MedlinePlus

... Fingerstick Devices Clinical Reminder: Insulin Pens Publications Infection Control Assessment of Ambulatory Surgical Centers Meetings Insurance Stakeholders Meeting – December 2011 Ambulatory Surgical Centers – October 2010 Safety by Design – May 2010 Sticking with Safety – May 2010 Injection ...

Knowledge and Practice on Injection Safety among Primary Health Care Workers in Kaski District, Western Nepal

PubMed Central

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, P Ravi; Kc, Vikash Kumar; Jha, Nisha; Sharma, Damodar

2016-01-01

Background Unsafe injection practice can transmit various blood borne infections. The aim of this study was to assess the knowledge and practice of injection safety among injection providers, to obtain information about disposal of injectable devices, and to compare the knowledge and practices of urban and rural injection providers. Methods The study was conducted with injection providers working at primary health care facilities within Kaski district, Nepal. Ninety-six health care workers from 69 primary health care facilities were studied and 132 injection events observed. A semi-structured checklist was used for observing injection practice and a questionnaire for the survey. Respondents were interviewed to complete the questionnaire and obtain possible explanations for certain observed behaviors. Results All injection providers knew of at least one pathogen transmitted through use/re-use of unsterile syringes. Proportion of injection providers naming hepatitis/jaundice as one of the diseases transmitted by unsafe injection practice was significantly higher in urban (75.6%) than in rural (39.2%) area. However, compared to urban respondents (13.3%), a significantly higher proportion of rural respondents (37.3%) named Hepatitis B specifically as one of the diseases transmitted. Median (inter-quartile range) number of therapeutic injection and injectable vaccine administered per day by the injection providers were 2 (1) and 1 (1), respectively. Two handed recapping by injection providers was significantly higher in urban area (33.3%) than in rural areas (21.6%). Most providers were not aware of the post exposure prophylaxis guideline. Conclusion The knowledge of the injection providers about safe injection practice was acceptable. The use of safe injection practice by providers in urban and rural health care facilities was almost similar. The deficiencies noted in the practice must be addressed. PMID:27540325

Safety syringes and anti-needlestick devices in orthopaedic surgery.

PubMed

Sibbitt, Wilmer L; Band, Philip A; Kettwich, Lawrence G; Sibbitt, Cristina R; Sibbitt, Lori J; Bankhurst, Arthur D

2011-09-07

The American Academy of Orthopaedic Surgery (AAOS), The Joint Commission, the Occupational Safety and Health Administration (OSHA), and the Needlestick Safety and Prevention Act encourage the integration of safety-engineered devices to prevent needlestick injuries to health-care workers and patients. We hypothesized that safety syringes and needles could be used in outpatient orthopaedic injection and aspiration procedures. The study investigated the orthopaedic uses and procedural idiosyncrasies of safety-engineered devices, including (1) four safety needles (Eclipse, SafetyGlide, SurGuard, and Magellan), (2) a mechanical safety syringe (RPD), (3) two automatic retractable syringes (Integra, VanishPoint), (4) three manual retractable syringes (Procedur-SF, Baksnap, Invirosnap), and (5) three shielded syringes (Safety-Lok, Monoject, and Digitally Activated Shielded [DAS] Syringe). The devices were first tested ex vivo, and then 1300 devices were used for 425 subjects undergoing outpatient arthrocentesis, intra-articular injections, local anesthesia, aspiration biopsy, and ultrasound-guided procedures. During the clinical observation, there were no accidental needlesticks (0 needlesticks per 1300 devices). Safety needles could be successfully used on a Luer syringe but were limited to ≤1.5 in (≤3.81 cm) in length and the shield could interfere with sonography. The mechanical safety syringes functioned well in all orthopaedic procedures. Automatic retractable syringes were too small for arthrocentesis of the knee, and the plunger blew out and prematurely collapsed with high-pressure injections. The manual retractable syringes and shielded syringes could be used with conventional needles for most orthopaedic procedures. The most effective and reliable safety devices for orthopaedic syringe procedures are shielded safety needles, mechanical syringes, manual retractable syringes, and shielded syringes, but not automatic retractable syringes. Even when adopting safety-engineered devices for an orthopaedic clinic, conventional syringes larger than 20 mL and conventional needles longer than 1.5 in (3.8 cm) are necessary.

Induction of Shock After Intravenous Injection of Adenovirus Vectors: A Critical Role for Platelet-activating Factor

PubMed Central

Xu, Zhili; Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.

2009-01-01

Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats with Ad5 vectors causes a novel rapid shock reaction that involves hypotension, hemoconcentration, tissue edema, and vasocongestion, with notable pathology in the pancreas and the gastrointestinal system. We show for the first time that this reaction is dependent on platelet-activating factor (PAF), a lipid signaling molecule that is a known shock inducer. Ad upregulated PAF within 5 minutes in vivo, and antagonists of the PAF receptor were able to prevent Ad-induced shock. Ad upregulated PAF via the reticuloendothelial system (RES), because splenectomy or depletion of phagocytes blocked the ability of Ad to induce both PAF and shock. Rats were considerably more sensitive to Ad-induced shock than were mice, but PAF mediated shock in both species. Other Ad-induced innate immune responses such as cytokine induction and thrombocytopenia were not mediated by PAF. In summary, systemic IV injection of Ad stimulates the RES to upregulate PAF within a matter of minutes, which results in shock. The identification of this novel pathway suggests strategies to improve the safety of systemic gene therapy with Ad vectors. PMID:19953082

A Phase I trial using local regional treatment, nonlethal irradiation, intratumoral and systemic polyinosinic-polycytidylic acid polylysine carboxymethylcellulose to treat liver cancer: in search of the abscopal effect

PubMed Central

de la Torre, Andrew N; Contractor, Sohail; Castaneda, Ismael; Cathcart, Charles S; Razdan, Dolly; Klyde, David; Kisza, Piotr; Gonzales, Sharon F; Salazar, Andres M

2017-01-01

Purpose To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant. Methods Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic “danger” response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years. Results Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients <60 years old, 2-year survival was 62.5% vs. 11.1% in patients aged >60 years (P<0.05). Several patients had prolonged PFS and OS. Conclusion Intra-tumoral injection of the TLR3 agonist poly-ICLC in patients with HCC is safe and tolerable when combined with local nonlethal radiation and local regional treatment. Further work is in progress to evaluate if this approach improves survival compared to local regional treatment alone and characterize changes in anticancer immunity. PMID:28848723

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

PubMed

Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

2015-03-01

Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.

21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea...

21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea...

21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea...

21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea...

Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer.

PubMed

Tchou, Julia; Zhao, Yangbing; Levine, Bruce L; Zhang, Paul J; Davis, Megan M; Melenhorst, Jan Joseph; Kulikovskaya, Irina; Brennan, Andrea L; Liu, Xiaojun; Lacey, Simon F; Posey, Avery D; Williams, Austin D; So, Alycia; Conejo-Garcia, Jose R; Plesa, Gabriela; Young, Regina M; McGettigan, Shannon; Campbell, Jean; Pierce, Robert H; Matro, Jennifer M; DeMichele, Angela M; Clark, Amy S; Cooper, Laurence J; Schuchter, Lynn M; Vonderheide, Robert H; June, Carl H

2017-12-01

Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602). Introducing the CAR construct via mRNA ensured safety by limiting the nontumor cell effects (on-target/off-tumor) of targeting c-Met. Patients with metastatic breast cancer with accessible cutaneous or lymph node metastases received a single intratumoral injection of 3 × 10 7 or 3 × 10 8 cells. CAR T mRNA was detectable in peripheral blood and in the injected tumor tissues after intratumoral injection in 2 and 4 patients, respectively. mRNA c-Met-CAR T cell injections were well tolerated, as none of the patients had study drug-related adverse effects greater than grade 1. Tumors treated with intratumoral injected mRNA c-Met-CAR T cells were excised and analyzed by immunohistochemistry, revealing extensive tumor necrosis at the injection site, cellular debris, loss of c-Met immunoreactivity, all surrounded by macrophages at the leading edges and within necrotic zones. We conclude that intratumoral injections of mRNA c-Met-CAR T cells are well tolerated and evoke an inflammatory response within tumors. Cancer Immunol Res; 5(12); 1152-61. ©2017 AACR . ©2017 American Association for Cancer Research.

Towards safe injection practices for prevention of hepatitis C transmission in South Asia: Challenges and progress

PubMed Central

Janjua, Naveed Zafar; Butt, Zahid Ahmad; Mahmood, Bushra; Altaf, Arshad

2016-01-01

AIM: To summarize the available information about injection use and its determinants in the South Asian region. METHODS: We searched published and unpublished literature on injection safety in South Asia published during 1995-2016 using the keywords “injection” “unsafe injection” and “immunization injection” and combined these with each of the countries and/or their respective states or provinces in South Asia. We used a standardized questionnaire to abstract the following data from the articles: the annual number of injections per capita, the proportion of injections administered with a reused syringe or needle, the distribution of injections with respect to prescribers and providers and determinants of injection use. RESULTS: Although information is very limited for certain countries (i.e., Bhutan, Maldives and Sri Lanka), healthcare injection use is very common across South Asia, with cross-country rates ranging from 2.4 to 13.6 injections/person/year. Furthermore, recent studies show that 5% to 50% of these injections are provided with reused syringes, thus creating potential to transmission of blood-borne pathogens. Qualified and unqualified practitioners, especially in the private sector, are the major drivers behind injection use, but patients also prefer injections, especially among the rural, poor or uneducated in certain countries. According to available data, Pakistan and India have recently taken steps towards achieving safe injection. Potential interventions include the introduction of reuse prevention devices, and patient-, community- and patient/community and provider-centered interventions to change population and practitioner behavior. CONCLUSION: Injection use is common in South Asian countries. Multilevel interventions aiming at patients, providers and the healthcare system are needed to reduce injection use and reuse. PMID:27433097

Motor vehicle technology:Mobility for prosperity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1985-01-01

This book presents the papers given at a conference on internal combustion engines for vehicles. Topics considered at the conference included combustion chambers, the lubrication of turbocharged engines, oil filters, fuel consumption, traffic control, crashworthiness, brakes, acceleration, unleaded gasoline, methanol fuels, pressure drop, safety regulations, tire vibration, detergents, fuel economy, ceramics in engines, steels, catalytic converters, fuel additives, heat exchangers, pump systems, emissions control, fuel injection systems, noise pollution control, natural gas fuels, assembly plant productivity, aerodynamics, torsion, electronics, and automatic transmissions.

Safety of Accelerated Schedules of Subcutaneous Allergen Immunotherapy with House Dust Mite Extract in Patients with Atopic Dermatitis

PubMed Central

Kim, Myoung-Eun; Kim, Jeong-Eun; Sung, Joon-Mo; Lee, Jin-Woo; Choi, Gil-Soon

2011-01-01

The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD. PMID:21935270

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study

PubMed Central

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

Purpose The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. Materials and methods The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4) in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. Main outcome measure(s) An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. Main results The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Conclusion Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention. PMID:25897212

Centrifugal Compressor Surge Margin Improved With Diffuser Hub Surface Air Injection

NASA Technical Reports Server (NTRS)

Skoch, Gary J.

2002-01-01

Aerodynamic stability is an important parameter in the design of compressors for aircraft gas turbine engines. Compression system instabilities can cause compressor surge, which may lead to the loss of an aircraft. As a result, engine designers include a margin of safety between the operating line of the engine and the stability limit line of the compressor. The margin of safety is typically referred to as "surge margin." Achieving the highest possible level of surge margin while meeting design point performance objectives is the goal of the compressor designer. However, performance goals often must be compromised in order to achieve adequate levels of surge margin. Techniques to improve surge margin will permit more aggressive compressor designs. Centrifugal compressor surge margin improvement was demonstrated at the NASA Glenn Research Center by injecting air into the vaned diffuser of a 4:1-pressure-ratio centrifugal compressor. Tests were performed using injector nozzles located on the diffuser hub surface of a vane-island diffuser in the vaneless region between the impeller trailing edge and the diffuser-vane leading edge. The nozzle flow path and discharge shape were designed to produce an air stream that remained tangent to the hub surface as it traveled into the diffuser passage. Injector nozzles were located near the leading edge of 23 of the 24 diffuser vanes. One passage did not contain an injector so that instrumentation located in that passage would be preserved. Several orientations of the injected stream relative to the diffuser vane leading edge were tested over a range of injected flow rates. Only steady flow (nonpulsed) air injection was tested. At 100 percent of the design speed, a 15-percent improvement in the baseline surge margin was achieved with a nozzle orientation that produced a jet that was bisected by the diffuser vane leading edge. Other orientations also improved the baseline surge margin. Tests were conducted at speeds below the design speed, and similar results were obtained. In most cases, the greatest improvement in surge margin occurred at fairly low levels of injected flow rate. Externally supplied injection air was used in these experiments. However, the injected flow rates that provided the greatest benefit could be produced using injection air that is recirculating between the diffuser discharge and nozzles located in the diffuser vaneless region. Future experiments will evaluate the effectiveness of recirculating air injection.

Ice Reduces Needle-Stick Pain Associated With Local Anesthetic Injection

PubMed Central

Mahshidfar, Babak; Cheraghi Shevi, Salimeh; Abbasi, Mohsen; Kasnavieh, Mohammad Hosseini; Rezai, Mahdi; Zavereh, Mina; Mosaddegh, Reza

2016-01-01

Background Local anesthetic injections are widely used in the emergency department for different purposes. Pain management for such injections is of great importance to both patients and the healthcare system. Objectives Our study aimed to determine the effectiveness and safety of cryotherapy in patients receiving local anesthetic injections. Methods Subjects who presented with superficial lacerations were randomly assigned to 2 groups, the first group received ice packing prior to injection and the second did not. The pain severity, length and depth of the laceration, and the other necessary information before and after the pain-reducing intervention were measured, documented, and compared at the end of the study. Pain scores were measured using a numerical rating scale before and after the procedure, and the differences were compared using a t-test. Results Ninety subjects were enrolled in the study, 45 in each group. There were no statistical differences between the 2 groups in terms of baseline preoperative and operative characteristics (P > 0.05). The pain scores in the cryotherapy group were significantly lower before and after the procedure (P < 0.001). There was no statistically significant difference between the 2 groups for wound infection (P = 0.783). Conclusions Cooling the injection site prior to local anesthetic injection is an effective and inexpensive method to reduce the pain and discomfort caused by the injection. PMID:27847696

Identification of protein components and quantitative immunoassay for SEC2 in staphylococcin injection.

PubMed

Ding, Ding; Huang, Peng; Sun, Hongying; Xue, Qiao; Pan, Yingqiu; Chen, Shuqing

2009-08-15

In China, staphylococcin injection has been commonly used in combined cancer therapy to enhance the systemic immune response and reduce the toxicities associated with chemotherapy or radiation therapy in the last decade. It is claimed that the main effective component is staphylococcal enterotoxin C2 (SEC2). However, no standard method based on the concentration of SEC2 has been established for quality control of the injection products. In this study, a sensitive and reliable biotin-streptavidin-ELISA (BS-ELISA) method was established for detection and quantification of SEC2. In addition, 1-D SDS-PAGE coupled with nano-LC-MS/MS was performed to identify the protein components in the injection products from one manufacturing company. The results of the BS-ELISA showed that SEC2 only accounted for less than 0.1% of the total protein in the injection products, and the nano-LC-MS/MS results showed that fifty-five proteins of Staphylococcus aureus were confidently identified in the injection solution. Seventeen out of these proteins, including SEC2, were well-known virulence factors. In addition, eighteen proteins of other Gram-positive bacteria were also confidently identified. Thus, the results indicated that SEC2 is of very low concentration in the injection products and the process of the injection preparation should be improved for health and safety consideration.

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

Performance and stability analysis of gas-injection enhanced natural circulation in heavy-liquid-metal-cooled systems

NASA Astrophysics Data System (ADS)

Yoo, Yeon-Jong

The purpose of this study is to investigate the performance and stability of the gas-injection enhanced natural circulation in heavy-liquid-metal-cooled systems. The target system is STAR-LM, which is a 400-MWt-class advanced lead-cooled fast reactor under development by Argonne National Laboratory and Oregon State University. The primary loop of STAR-LM relies on natural circulation to eliminate main circulation pumps for enhancement of passive safety. To significantly increase the natural circulation flow rate for the incorporation of potential future power uprates, the injection of noncondensable gas into the coolant above the core is envisioned ("gas lift pump"). Reliance upon gas-injection enhanced natural circulation raises the concern of flow instability due to the relatively high temperature change in the reactor core and the two-phase flow condition in the riser. For this study, the one-dimensional flow field equations were applied to each flow section and the mixture models of two-phase flow, i.e., both the homogeneous and drift-flux equilibrium models were used in the two-phase region of the riser. For the stability analysis, the linear perturbation technique based on the frequency-domain approach was used by employing the Nyquist stability criterion and a numerical root search method. It has been shown that the thermal power of the STAR-LM natural circulation system could be increased from 400 up to 1152 MW with gas injection under the limiting void fraction of 0.30 and limiting coolant velocity of 2.0 m/s from the steady-state performance analysis. As the result of the linear stability analysis, it has turned out that the STAR-LM natural circulation system would be stable even with gas injection. In addition, through the parametric study, it has been found that the thermal inertia effects of solid structures such as fuel rod and heat exchanger tube should be considered in the stability analysis model. The results of this study will be a part of the optimized stable design of the gas-injection enhanced natural circulation of STAR-LM with substantially improved power level and economical competitiveness. Furthermore, combined with the parametric study, this research could contribute a guideline for the design of other similar heavy-liquid-metal-cooled natural circulation systems with gas injection.

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe?

PubMed

Kruse, David W

2008-12-01

Osteoarthritis of the hip is a significant source of morbidity in the elderly. Treatment guidelines are available for the management of hip osteoarthritis, but these do not address the application of intraarticular corticosteroid injection. The intraarticular injection of corticosteroid is used in the management of other large joint osteoarthritic diseases and is well studied in the knee, however, this data cannot be used to make sound clinical decisions regarding its use for hip osteoarthritis. There are also concerns regarding the safety of this modality. Review of the published literature reveals that there are eight trials examining the efficacy of intraarticular corticosteroid injection for hip osteoarthritis and of these only four are randomized controlled trials. In general, the available literature demonstrates a short-term reduction of pain with corticosteroid injection and is indicated for patients refractory to non-pharmacologic or analgesic and NSAID therapy. The use of radiologic-guidance is recommended and, with proper sterile technique, the risk of adverse outcomes is very low. Future randomized controlled trials are needed to further examine the efficacy and safety of intraarticular corticosteroid injection for hip osteoarthritis.

Ab interno trabecular bypass surgery with iStent for open angle glaucoma

PubMed Central

Le, Jimmy T; Bicket, Amanda K; Li, Tianjing

2018-01-01

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective is to assess the comparative effectiveness and safety of ab interno trabecular bypass surgery with iStent or iStent inject for OAG in comparison to conventional medical, laser, or surgical treatment. A secondary objective is to examine the effectiveness and safety of iStent or iStent Inject surgery in people who have concomitant phacoemulsification. PMID:27526051

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia

PubMed Central

Gen, Keishi; Takahashi, Yuki

2013-01-01

Objective: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose. Methods: The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests. Results: The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups. Conclusion: The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol. PMID:24294484

Reduced injection pressures using a compressed air injection technique (CAIT): an in vitro study.

PubMed

Tsui, Ban C H; Knezevich, Mark P; Pillay, Jennifer J

2008-01-01

High injection pressures have been associated with intraneural injection and persistent neurological injury in animals. Our objective was to test whether a reported simple compressed air injection technique (CAIT) would limit the generation of injection pressures to below a suggested 1,034 mm Hg limit in an in vitro model. After ethics board approval, 30 consenting anesthesiologists injected saline into a semiclosed system. Injection pressures using 30 mL syringes connected to a 22 gauge needle and containing 20 mL of saline were measured for 60 seconds using: (1) a typical "syringe feel" method, and (2) CAIT, thereby drawing 10 mL of air above the saline and compressing this to 5 mL prior to and during injections. All anesthesiologists performed the syringe feel method before introduction and demonstration of CAIT. Using CAIT, no anesthesiologist generated pressures above 1,034 mm Hg, while 29 of 30 produced pressures above this limit at some time using the syringe feel method. The mean pressure using CAIT was lower (636 +/- 71 vs. 1378 +/- 194 mm Hg, P = .025), and the syringe feel method resulted in higher peak pressures (1,875 +/- 206 vs. 715 +/- 104 mm Hg, P = .000). This study demonstrated that CAIT can effectively keep injection pressures under 1,034 mm Hg in this in vitro model. Animal and clinical studies will be needed to determine whether CAIT will allow objective, real-time pressure monitoring. If high pressure injections are proven to contribute to nerve injury in humans, this technique may have the potential to improve the safety of peripheral nerve blocks.

Driving magnetic turbulence using flux ropes in a moderate guide field linear system

NASA Astrophysics Data System (ADS)

Brookhart, Matthew I.; Stemo, Aaron; Waleffe, Roger; Forest, Cary B.

2017-12-01

We present a series of experiments on novel, line-tied plasma geometries as a study of the generation of chaos and turbulence in line-tied systems. Plasma production and the injection scale for magnetic energy is provided by spatially discrete plasma guns that inject both plasma and current. The guns represent a technique for controlling the injection scale of magnetic energy. A two-dimensional (2-D) array of magnetic probes provides spatially resolved time histories of the magnetic fluctuations at a single cross-section of the experimental cylinder, allowing simultaneous spatial measurements of chaotic and turbulent behaviour. The first experiment shows chaotic fluctuations and self-organization in a hollow-current line-tied screw pinch. These dynamics is modulated primarily by the applied magnetic field and weakly by the plasma current and safety factor. The second experiment analyses the interactions of multiple line-tied flux ropes. The flux ropes all exhibit chaotic behaviour, and under certain conditions develop an inverse cascade to larger scales and a turbulent inertial range with magnetic energy ( ) related to perpendicular wave number ( \\bot $ ) as \\bot -2.5\\pm 0.5$ .

Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis.

PubMed

Lee, Jin Kyu; Choi, Chong-Hyuk; Oh, Kwang-Jun; Kyung, Hee-Soo; Yoo, Ju-Hyung; Ha, Chul-Won; Bin, Seong-Il; Kang, Seung-Baik; Kim, Myung Ku; Lee, Ju-Hong; Lee, Myung Chul

2017-11-01

The objective of this study is to assess the safety and efficacy of repeated intra-articular injection of high molecular weight hyaluronic acid (LBSA0103) at a 26-week interval, in patients with osteoarthritis of the knee. The study was an open-label, single arm, multicentre prospective trial conducted in patients with symptomatic knee osteoarthritis. The intervention consisted of two intra-articular injections of LBSA0103, with the second injection performed 26 weeks after the first injection. The primary outcome was the incidence of adverse drug reactions related to each injection. Assessment of efficacy of repeated injections in terms of maintenance of pain relief was a secondary objective of this study. Of the 185 patients screened, 174 patients received the first injection and 153 patients received both injections of LBSA0103. Nine adverse drug reactions occurred in seven patients (4.02%) after the first injection, while only one adverse drug reaction occurred (0.65%) after the second injection. As a secondary outcome measure, the improvements in the efficacy parameters including total WOMAC score and weight-bearing pain were all significant at both week 13 and 39 compared to the baseline value (P < 0.001), and improvements after the second injection were consistent with those after the initial injection of LBSA0103 (between week 26 and week 39, P < 0.001). Repeated intra-articular injection of LBSA0103 at a 26-week interval is safe without increased risk of adverse drug reactions. Additionally, LBSA0103 is effective in reduction of osteoarthritis knee pain and in maintenance of pain reduction for a 39-week period when a second injection is administered.

Safe use of epidural corticosteroid injections: recommendations of the WIP Benelux workgroup.

PubMed

Van Boxem, Koen; Rijsdijk, Mienke; Hans, Guy; de Jong, Jasper; Kallewaard, Jan Willem; Vissers, Kris; van Kleef, Maarten; Rathmell, James P; Van Zundert, Jan

2018-05-14

Epidural corticosteroid injections are used frequently worldwide in the treatment of radicular pain. Concerns have risen involving rare major neurologic injuries after this treatment. Recommendations to prevent these complications have been published, but local implementation is not always feasible due to local circumstances and necessitating local recommendations based on literature review. A workgroup of 4 stakeholder pain societies in Belgium, The Netherlands and Luxembourg (Benelux) has reviewed the literature involving neurological complications after epidural corticosteroid injections and possible safety measures to prevent these major neurologic injuries. Twenty-six considerations and recommendations were selected by the workgroup. These involve the use of imaging, injection equipment particulate and non-particulate corticosteroids, epidural approach and maximal volume to be injected. Raising awareness about possible neurological complications and adoption of safety measures recommended by the work group aim at reducing the risks of these devastating events. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fast Time Response Electromagnetic Particle Injection System for Disruption Mitigation

NASA Astrophysics Data System (ADS)

Raman, Roger; Lay, W.-S.; Jarboe, T. R.; Menard, J. E.; Ono, M.

2017-10-01

Predicting and controlling disruptions is an urgent issue for ITER. In this proposed method, a radiative payload consisting of micro spheres of Be, BN, B, or other acceptable low-Z materials would be injected inside the q =2 surface for thermal and runaway electron mitigation. The radiative payload would be accelerated to the required velocities (0.2 to >1km/s) in an Electromagnetic Particle Injector (EPI). An important advantage of the EPI system is that it could be positioned very close to the reactor vessel. This has the added benefit that the external field near a high-field tokamak dramatically improves the injector performance, while simultaneously reducing the system response time. A NSTX-U / DIII-D scale system has been tested off-line to verify the critical parameters - the projected system response time and attainable velocities. Both are consistent with the model calculations, giving confidence that an ITER-scale system could be built to ensure safety of the ITER device. This work is supported by U.S. DOE Contracts: DE-AC02-09CH11466, DE-FG02-99ER54519 AM08, and DE-SC0006757.

Intravitreal, Subretinal, and Suprachoroidal Injections: Evolution of Microneedles for Drug Delivery.

PubMed

Hartman, Rachel R; Kompella, Uday B

Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With the introduction of new therapeutic agents, this number is expected to increase. In addition, drug products that are injectable in ocular compartments other than the vitreous humor are expected to enter the back of the eye market in the not so distant future. Besides the IVT route, some of the most actively investigated routes of invasive administration to the eye include periocular, subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the driving force behind new injectable drug product development for the eye, safety is also being improved with time. In the case of IVT injections, the procedural guidelines have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Similar advances are anticipated for other routes of administration of injectable products to the eye. In addition to procedural improvements, the design of needles, particularly those with smaller diameters, length, and controlled bevel angles are expected to improve overall safety and acceptance of injected ophthalmic drug products. A key development in this area is the introduction of microneedles of a length less than a millimeter that can target the SC space. In the future, needles with smaller diameters and lengths, potentially approaching nanodimensions, are expected to revolutionize ophthalmic disease management.

Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine

PubMed Central

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-01-01

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydrops fetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important. PMID:21807052

Safety of intra-articular transplantation of lentivirally transduced mesenchymal stromal cells for haemophilic arthropathy in a non-human primate.

PubMed

Ohmori, Tsukasa; Mizukami, Hiroaki; Katakai, Yuko; Kawai, Sho; Nakamura, Hitoyasu; Inoue, Makoto; Shu, Tsugumine; Sugimoto, Hideharu; Sakata, Yoichi

2018-05-08

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11-16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients.

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

30 CFR 250.124 - Will BSEE approve gas injection into the cap rock containing a sulphur deposit?

Code of Federal Regulations, 2012 CFR

2012-07-01

... rock containing a sulphur deposit? 250.124 Section 250.124 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF General Performance Standards § 250.124 Will BSEE approve gas injection into the cap rock containing a sulphur deposit? To receive the Regional Supervisor's approval to inject gas into the cap rock...

30 CFR 250.124 - Will BSEE approve gas injection into the cap rock containing a sulphur deposit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... rock containing a sulphur deposit? 250.124 Section 250.124 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF General Performance Standards § 250.124 Will BSEE approve gas injection into the cap rock containing a sulphur deposit? To receive the Regional Supervisor's approval to inject gas into the cap rock...

30 CFR 250.124 - Will BSEE approve gas injection into the cap rock containing a sulphur deposit?

Code of Federal Regulations, 2014 CFR

2014-07-01

... rock containing a sulphur deposit? 250.124 Section 250.124 Mineral Resources BUREAU OF SAFETY AND... CONTINENTAL SHELF General Performance Standards § 250.124 Will BSEE approve gas injection into the cap rock containing a sulphur deposit? To receive the Regional Supervisor's approval to inject gas into the cap rock...

Enhanced tolerance and antitumor efficacy by docetaxel-loaded albumin nanoparticles.

PubMed

Tang, Xiaolei; Wang, Guijun; Shi, Runjie; Jiang, Ke; Meng, Lingtong; Ren, Hao; Wu, Jinhui; Hu, Yiqiao

2016-10-01

Docetaxel is one of the most active chemotherapeutic agents for cancer treatment. The traditional docetaxel injection (TAXOTERE®) is currently formulated in the surfactant polysorbate 80, which has been associated with severe adverse reactions. To avoid the use of polysorbate 80 as well as to reduce the systemic toxicity of docetaxel, in this study, docetaxel-loaded albumin nanoparticles were fabricated by a novel simple self-assembly method. The resulting nanoparticles showed a mean diameter size of 150 nm. After being encapsulated into nanoparticles, docetaxel displayed similar cytotoxicity to traditional injection. Since polysorbate 80 was not involved in nanoparticles, the hemolysis was completely eliminated. The maximal tolerance dose of nanoparticles was also increased, which allowed a higher dose to be safely intravenously injected and produced ideal antitumor effects. The 150 nm diameter also allowed the nanoparticles to accumulate in tumor tissue via the enhanced permeability and retention effect. The passive targeting ability further caused the higher antitumor effects of nanoparticles than that of traditional injection at the same dose (7.5 mg/kg). Therefore, docetaxel-loaded albumin nanoparticles fabricated by our strategy showed higher promise in their safety and effectiveness than the traditional docetaxel injection.

Effect of injection routes on the biodistribution, clearance, and tumor uptake of carbon dots.

PubMed

Huang, Xinglu; Zhang, Fan; Zhu, Lei; Choi, Ki Young; Guo, Ning; Guo, Jinxia; Tackett, Kenneth; Anilkumar, Parambath; Liu, Gang; Quan, Qimeng; Choi, Hak Soo; Niu, Gang; Sun, Ya-Ping; Lee, Seulki; Chen, Xiaoyuan

2013-07-23

The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the in vivo kinetic behaviors of these particles that are necessary for clinical translation are poorly understood to date. In this study, fluorescent carbon dots (C-dots) were synthesized and the effect of three injection routes on their fate in vivo was explored by using both near-infrared fluorescence and positron emission tomography imaging techniques. We found that C-dots are efficiently and rapidly excreted from the body after all three injection routes. The clearance rate of C-dots is ranked as intravenous > intramuscular > subcutaneous. The particles had relatively low retention in the reticuloendothelial system and showed high tumor-to-background contrast. Furthermore, different injection routes also resulted in different blood clearance patterns and tumor uptakes of C-dots. These results satisfy the need for clinical translation and should promote efforts to further investigate the possibility of using carbon-based nanoprobes in a clinical setting. More broadly, we provide a testing blueprint for in vivo behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles.

Immunogenicity and safety of zoster vaccine live administered with quadrivalent influenza virus vaccine.

PubMed

Levin, Myron J; Buchwald, Ulrike K; Gardner, Julie; Martin, Jason; Stek, Jon E; Brown, Elizabeth; Popmihajlov, Zoran

2018-01-02

Randomized, blinded, placebo-controlled trial to evaluate the safety and immunogenicity of ZOSTAVAX™ (ZV) administered concomitantly with quadrivalent inactivated influenza vaccine (IIV4) in adults≥50years of age (NCT02519855). Overall, 440 participants were randomized into the Concomitant Group (CG) and 442 into the Sequential Group (SG). The CG received ZV and IIV4 at separate injection sites on Day 1 and matching placebo at Week 4. The SG received placebo and IIV4 (2015-2016 influenza season) at separate injection sites on Day 1 and ZV at Week 4. Varicella-zoster virus (VZV) antibody geometric mean titer (GMT) and geometric mean fold-rise (GMFR) from baseline to 4weeks postvaccination, measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and adjusted for age and prevaccination titer. Influenza strain-specific GMT at baseline and 4weeks postvaccination was measured by hemagglutination inhibition (HAI) assay. Injection-site and systemic adverse experiences (AEs) within 28days following any vaccination and serious AEs throughout the study. The adjusted VZV antibody GMT ratio (CG/SG) was 0.87 (95%CI: 0.80, 0.95), meeting the prespecified noninferiority criterion. The VZV antibody GMFR in the CG was 1.9 (95%CI: 1.76, 2.05), meeting the acceptability criterion. Influenza antibody GMT ratios for A/H1N1, A/H3N2, B/Yamagata and B/Victoria were 1.02 (95%CI: 0.88, 1.18), 1.10 (95%CI: 0.94, 1.29), 1.00 (95%CI: 0.88, 1.14), and 0.99 (95%CI: 0.87, 1.13), respectively. The frequency of vaccine-related injection-site and systemic AEs was comparable between groups. No vaccine-related serious AE was observed. The concomitant administration of ZV and IIV4 to adults≥50years of age induced VZV-specific and influenza-specific antibody responses that were comparable to those following administration of either vaccine alone, and was generally well tolerated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety Study: Intraventricular Injection of a Modified Oncolytic Measles Virus into Measles-Immune, hCD46-Transgenic, IFNαRko Mice.

PubMed

Lal, Sangeet; Peng, Kah-Whye; Steele, Michael B; Jenks, Nathan; Ma, Hong; Kohanbash, Gary; Phillips, Joanna J; Raffel, Corey

2016-12-01

The modified Edmonston vaccine strain of measles virus (MV) has shown potent oncolytic efficacy against various tumor types and is being investigated in clinical trials. Our laboratory showed that MV effectively kills medulloblastoma tumor cells in both localized disease and when tumor cells are disseminated through cerebrospinal fluid (CSF). Although the safety of repeated intracerebral injection of modified MV in rhesus macaques has been established, the safety of administering MV into CSF has not been adequately investigated. In this study, we assessed the safety of MV-NIS (MV modified to express the human sodium iodide symporter protein) injected into the CSF of measles-immunized and measles virus-susceptible transgenic (CD46, IFNαRko) mice. Treated animals were administered a single intraventricular injection of 1 × 10 5 or 1 × 10 6 TCID 50 (50% tissue culture infective dose) of MV-NIS. Detailed clinical observation was performed over a 90-day period. Clinically, we did not observe any measles-related toxic effects or behavioral abnormality in animals of any treated cohort. The complete blood count and blood chemistry analysis results were found to be within normal range for all the cohorts. Histologic examination of brains and spinal cords revealed inflammatory changes, mostly related to the needle track; these resolved by day 21 postinjection. To assess viral biodistribution, quantitative RT-PCR to detect the measles virus N-protein was performed on blood and brain samples. Viral RNA was not detectable in the blood as soon as 2 days after injection, and virus cleared from the brain by 45 days postadministration in all treatment cohorts. In conclusion, our data suggest that a single injection of modified MV into the CSF is safe and can be used in future therapeutic applications.

Efficacy and safety of acute injection laryngoplasty for vocal cord paralysis following thoracic surgery.

PubMed

Graboyes, Evan M; Bradley, Joseph P; Meyers, Bryan F; Nussenbaum, Brian

2011-11-01

The primary objective of this study was to evaluate the effectiveness and safety of injection laryngoplasty using a temporary injectable agent in the acute setting for patients with unilateral vocal cord paralysis following thoracic surgical procedures. Retrospective consecutive case series in an academic institution. Inclusion criteria included patients acutely treated with injection laryngoplasty from January 1, 2006, to March 31, 2010, for a unilateral vocal cord paralysis that occurred after a thoracic surgical procedure (N = 20). All patients were injected with Radiesse Voice Gel using microlaryngoscopy technique. The mean time to vocal cord injection from the time of thoracic surgery was 4.5 days. There was one operative-related complication of intraoperative bile reflux that caused a pneumonitis. Ninety percent of patients were recommended for strict nothing by mouth prior to injection. Of these, 94% were allowed an oral diet following injection, and 67% tolerated a regular diet. None of the patients required subsequent procedures for aspiration or dysphagia, and 25% required further intervention after discharge for persistent dysphonia. Patients with a known nerve transection had a higher rate of dysphonia requiring further surgical procedures than those who did not have a known nerve transection. Acute treatment of thoracic surgery-related unilateral vocal cord paralysis with injection laryngoplasty appears safe and effective at preventing postoperative aspiration pneumonia and improves swallowing function to allow resumption of an oral diet. A single injection is often the only required treatment. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Rapid assessment of injection practices in Cambodia, 2002

PubMed Central

Vong, Sirenda; Perz, Joseph F; Sok, Srun; Som, Seiharath; Goldstein, Susan; Hutin, Yvan; Tulloch, James

2005-01-01

Background Injection overuse and unsafe injection practices facilitate transmission of bloodborne pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Anecdotal reports of unsafe and unnecessary therapeutic injections and the high prevalence of HBV (8.0%), HCV (6.5%), and HIV (2.6%) infection in Cambodia have raised concern over injection safety. To estimate the magnitude and patterns of such practices, a rapid assessment of injection practices was conducted. Methods We surveyed a random sample of the general population in Takeo Province and convenience samples of prescribers and injection providers in Takeo Province and Phnom Penh city regarding injection-related knowledge, attitudes, and practices. Injection providers were observed administering injections. Data were collected using standardized methods adapted from the World Health Organization safe injection assessment guidelines. Results Among the general population sample (n = 500), the overall injection rate was 5.9 injections per person-year, with 40% of participants reporting receipt of ≥ 1 injection during the previous 6 months. Therapeutic injections, intravenous infusions, and immunizations accounted for 74%, 16% and 10% of injections, respectively. The majority (>85%) of injections were received in the private sector. All participants who recalled their last injection reported the injection was administered with a newly opened disposable syringe and needle. Prescribers (n = 60) reported that 47% of the total prescriptions they wrote included a therapeutic injection or infusion. Among injection providers (n = 60), 58% recapped the syringe after use and 13% did not dispose of the used needle and syringe appropriately. Over half (53%) of the providers reported a needlestick injury during the previous 12 months. Ninety percent of prescribers and injection providers were aware HBV, HCV, and HIV were transmitted through unsafe injection practices. Knowledge of HIV transmission through "dirty" syringes among the general population was also high (95%). Conclusion Our data suggest that Cambodia has one of the world's highest rates of overall injection usage, despite general awareness of associated infection risks. Although there was little evidence of reuse of needles and syringes, support is needed for interventions to address injection overuse, healthcare worker safety and appropriate waste disposal. PMID:15929800

The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

PubMed

Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

2017-08-03

Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.

Safety and immunogenicity of a new chromatographically purified rabies vaccine in comparison to the human diploid cell vaccine.

PubMed

Arora, Ashoni; Moeller, Larry; Froeschle, James

2004-01-01

Although human diploid cell vaccine (HDCV) has been available for over two decades and has a proven record of efficacy, it is very expensive to produce and can only be made in small quantities. In this trial, we compared the safety and immunogenicity of a new, chromatographically purified rabies vaccine (CPRV) with those of HDCV. One hundred and thirty-five healthy veterinary students were randomized in a 2:1 ratio between CPRV and HDCV respectively. Each student subsequently received an intramuscular injection of 0.5 mL of CPRV or 1mL of HDCV on days 0, 7, and 28, according to the standard preexposure regimen. Local safety data were collected for 7 days following each dose and systemic safety data for 42 days following the first dose. Vaccine administration and safety evaluation were performed by different site personnel. Sera for immunogenicity analysis were collected on days 0 (prevaccination), 28 and 42. All subjects achieved an antirabies antibody titer greater than or equal to the World Health Organization (WHO) accepted threshold level of seroconversion of 0.5 IU/mL after only two of three doses of vaccine in both groups. The geometric mean titers (IU/mL) in the CPRV and HDCV groups respectively were 6.54 (range 0.50 to 64.80) and 10.22 (range 0.70 to 51.40) on day 28, and 40.51 (range 5.40 to 278.00) and 37.71 (range 5.40 to 278.00) on day 42. The percentage of subjects experiencing local reactions within 3 days after any dose ranged from 65.2% to 80.9% in the CPRV group and from 77.3% to 84.4% in the HDCV group. The local reaction reported by the greatest percentage of subjects after each dose was pain/tenderness at the injection site, and most reactions were mild. Most of the reported local reactions resolved within 0 to 3 days postvaccination. Systemic reactions decreased from 76.4% after dose 1 to 36.0% after dose 3 in the CPRV group, and similarly from 55.6% to 31.8% in the HDCV group. For all postdose periods, the systemic reaction reported by the highest percentage of subjects was myalgia. No subjects experienced an immediate local or systemic reaction. In healthy adults, vaccination with CPRV using a preexposure schedule resulted in a safety and immunogenicity profile similar to that of HDCV.

Casting Molding of PDCPD Material for Purpose of Car’s Power Steering Body

NASA Astrophysics Data System (ADS)

Grabowski, L.; Baier, A.; Sobek, M.

2018-01-01

The growing industry of polymer and composite materials is facing new challenges posed by the automotive industry. In this industry, traditional materials such as steel and aluminum are widely replaced with plastic materials, including polymers. In the past, such behavior concerned design and interior elements, but more and more often plastics are used in the case of load-bearing elements, i.e. those that require high strength and durability nowadays. This kind of materials are also often used in safety systems or driver assistance systems. Therefore, the aim of the activities described in this article are to carry out an innovative process of injection of cold polymeric material, PDCPD (Polidicyclopentadiene), polymerizing with the use of Metathesis reaction, which in 2005 was awarded the Nobel Prize. This injection applies to the worm gear components of the system, supports the power steering system of the passenger car. Also the process of selecting the appropriate parameters to carry out this process, guaranteeing the best quality of the obtained elements is necessary. The aim of the activities was to achieve a fully useful power steering support system, using a polymer body, which is replacing the aluminum. These activities were aimed at reducing the costs and weight of the final product. The injection process and the way to achieve the finished product were carried out in an innovative way, never used in industry before.

Safety and Immunogenicity of PENNVAX-G DNA Prime Administered by Biojector 2000 or CELLECTRA Electroporation Device With Modified Vaccinia Ankara-CMDR Boost.

PubMed

Ake, Julie A; Schuetz, Alexandra; Pegu, Poonam; Wieczorek, Lindsay; Eller, Michael A; Kibuuka, Hannah; Sawe, Fredrick; Maboko, Leonard; Polonis, Victoria; Karasavva, Nicos; Weiner, David; Sekiziyivu, Arthur; Kosgei, Josphat; Missanga, Marco; Kroidl, Arne; Mann, Philipp; Ratto-Kim, Silvia; Anne Eller, Leigh; Earl, Patricia; Moss, Bernard; Dorsey-Spitz, Julie; Milazzo, Mark; Laissa Ouedraogo, G; Rizvi, Farrukh; Yan, Jian; Khan, Amir S; Peel, Sheila; Sardesai, Niranjan Y; Michael, Nelson L; Ngauy, Viseth; Marovich, Mary; Robb, Merlin L

2017-11-27

We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, followed by a double-blind, placebo-controlled part B in East Africa. Solicited and unsolicited adverse events were recorded, and immune responses were measured. Eighty-eight of 100 enrolled participants completed all study injections, which were generally safe and well tolerated, with more immediate, but transient, pain in the electroporation group. Cellular responses were observed in 57% of vaccine recipients tested and were CD4 predominant. High rates of binding antibody responses to CRF01_AE antigens, including gp70 V1V2 scaffold, were observed. Neutralizing antibodies were detected in a peripheral blood mononuclear cell assay, and moderate antibody-dependent, cell-mediated cytotoxicity activity was demonstrated. The PVG/MVA-CMDR HIV-1 vaccine regimen is safe and immunogenic. Substantial differences in safety or immunogenicity between modes of DNA delivery were not observed. NCT01260727. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A mobile robot system for ground servicing operations on the space shuttle

NASA Astrophysics Data System (ADS)

Dowling, K.; Bennett, R.; Blackwell, M.; Graham, T.; Gatrall, S.; O'Toole, R.; Schempf, H.

1992-11-01

A mobile system for space shuttle servicing, the Tessellator, has been configured, designed and is currently being built and integrated. Robot tasks include chemical injection and inspection of the shuttle's thermal protection system. This paper outlines tasks, rationale, and facility requirements for the development of this system. A detailed look at the mobile system and manipulator follow with a look at mechanics, electronics, and software. Salient features of the mobile robot include omnidirectionality, high reach, high stiffness and accuracy with safety and self-reliance integral to all aspects of the design. The robot system is shown to meet task, facility, and NASA requirements in its design resulting in unprecedented specifications for a mobile-manipulation system.

A mobile robot system for ground servicing operations on the space shuttle

NASA Technical Reports Server (NTRS)

Dowling, K.; Bennett, R.; Blackwell, M.; Graham, T.; Gatrall, S.; O'Toole, R.; Schempf, H.

1992-01-01

A mobile system for space shuttle servicing, the Tessellator, has been configured, designed and is currently being built and integrated. Robot tasks include chemical injection and inspection of the shuttle's thermal protection system. This paper outlines tasks, rationale, and facility requirements for the development of this system. A detailed look at the mobile system and manipulator follow with a look at mechanics, electronics, and software. Salient features of the mobile robot include omnidirectionality, high reach, high stiffness and accuracy with safety and self-reliance integral to all aspects of the design. The robot system is shown to meet task, facility, and NASA requirements in its design resulting in unprecedented specifications for a mobile-manipulation system.

Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review.

PubMed

Emile, Sameh Hany; Elfeki, Hossam Ayman; Elbanna, Hosam Ghazy; Youssef, Mohamed; Thabet, Waleed; Abd El-Hamed, Tito M; Said, Basem; Lotfy, Ahmed

2016-08-06

To evaluate the efficacy and safety of botulinum toxin type A (BTX-A) in the management of patients with anismus. An organized search of published literature was conducted using electronic databases including: PubMed/MEDLINE, and Cochrane Central Register of Controlled Trials, also an internet-based search using "Google Scholar" service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and long-term clinical improvement, post-injection changes in electromyography (EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection. Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU (range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonography-guided technique, one study used EMG-guided technique, whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4% (range 37.5%-86.7%), this percentage declined to a median of 46% (range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between (37.5%-80%), (54%-86.7%), and (25%-86.6%), respectively. Fourteen (7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. Initial satisfactory improvement of symptoms after BTX-A injection remarkably deteriorated after 3 mo of the procedure. However, repeated injection may provide better sustained results with no additional morbidities. Further analysis of more patients is necessary to conclude the safety of BTX-A for the treatment of anismus.

Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review

PubMed Central

Emile, Sameh Hany; Elfeki, Hossam Ayman; Elbanna, Hosam Ghazy; Youssef, Mohamed; Thabet, Waleed; Abd El-Hamed, Tito M; Said, Basem; Lotfy, Ahmed

2016-01-01

AIM: To evaluate the efficacy and safety of botulinum toxin type A (BTX-A) in the management of patients with anismus. METHODS: An organized search of published literature was conducted using electronic databases including: PubMed/MEDLINE, and Cochrane Central Register of Controlled Trials, also an internet-based search using “Google Scholar” service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and long-term clinical improvement, post-injection changes in electromyography (EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection. RESULTS: Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU (range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonography-guided technique, one study used EMG-guided technique, whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4% (range 37.5%-86.7%), this percentage declined to a median of 46% (range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between (37.5%-80%), (54%-86.7%), and (25%-86.6%), respectively. Fourteen (7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. CONCLUSION: Initial satisfactory improvement of symptoms after BTX-A injection remarkably deteriorated after 3 mo of the procedure. However, repeated injection may provide better sustained results with no additional morbidities. Further analysis of more patients is necessary to conclude the safety of BTX-A for the treatment of anismus. PMID:27602248

Analysis of efficacy and safety of treatment with collagenase Clostridium histolyticum among subgroups of patients with Dupuytren contracture.

PubMed

Raven, Raymond B; Kushner, Harvey; Nguyen, Dat; Naam, Nash; Curtin, Catherine

2014-09-01

Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patients with metacarpophalangeal (n = 167) or proximal interphalangeal (n = 104) joint contractures greater than or equal to 20 degrees treated with CCH (0.58 mg collagenase per injection). Subgroups included age, sex, and diabetes status. End points included rate of clinical success (reduction in contracture to 0-5 degrees of normal) and percentage of adverse events.There was no significant difference in clinical success by age, diabetes status, or sex with 63% reaching the end point. There was no difference in adverse events among the subgroups, with peripheral edema, contusion, and injection-site hemorrhage being most common.High-risk subgroups do not demonstrate differences in efficacy or safety with CCH treatment of Dupuytren-related contractures.

Human adipose-derived mesenchymal stem cells for osteoarthritis: a pilot study with long-term follow-up and repeated injections.

PubMed

Song, Yang; Du, Hui; Dai, Chengxiang; Zhang, Li; Li, Suke; Hunter, David J; Lu, Liangjing; Bao, Chunde

2018-04-01

This study aimed to evaluate the safety and therapeutic potential of autologous human adipose-derived mesenchymal stem cells (haMSCs) in patients with osteoarthritis. Safety and efficacy of haMSCs were preclinically assessed in vitro and in BALB/c-nu nude mice. 18 patients were enrolled and divided into three dose groups: the low-dose, mid-dose and high-dose group (1 × 10 7 , 2 × 10 7 and 5 × 10 7 cells, respectively), provided three injections and followed up for 96 weeks. The preclinical study established the safety and efficacy of haMSCs. Intra-articular injections of haMSCs were safe and improved pain, function and cartilage volume of the knee joint, rendering them a promising novel treatment for knee osteoarthritis. The dosage of 5 × 10 7 haMSCs exhibited the highest improvement (ClinicalTrials.gov Identifier: NCT01809769).

Safety of Lienal Polypeptide Injection Combined with Chemotherapy in Treating Patients with Advanced Cancer.

PubMed

Huang, Xin-En; Wang, Lin; Ji, Zhu-Qing; Liu, Meng-Yan; Qian, Ting; Li, Li

2015-01-01

To assess the safety of Liena polypeptide injection (produced by JILIN FSENS PHARMACEUTICAL CO.,LTD) combined with chemotherapy in treating patients with advanced cancers. A consecutive cohort of patients with advanced cancers were treated with Liena polypeptide injection combined with chemotherapy. And chemotherapy for patients with advanced cancers were adopted from regimens suggested by NCCN guideline. Liena polypeptide injection was intravenously injected at a dosage of 2 ml plus 100ml normal saline for continuous 7 days during chemotherapy as one course. After at least two courses of treatment, safety and side effects were evaluated. There were 20 female and 14 male patients with advanced cancer recruited into this study, including 10 patients with breast, 8 patients with colorectal, 8 patients with lung, 4 patients with gastric, and 1 patient with esophageal cancer, as well as 1 patient with non-Hodgkin's lymphoma, 1 patient with low pharyngeal and 1 patient with urethral cancer. The median age of patients was 59 (40-82) years. Incidences of Grade 1 to 2 myelosuppression was observed in 5/34 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 3/34 patients. Adverse effects on the gastrointestinal tract were documented in 5/34 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Liena polypeptide injection combined with chemotherapy was safe in treating several sites of tumors, that mainly included lung, colorectal and breast cancer. However, further study should be conducted to clarify the effectiveness of this treatment.

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

PubMed

Barbero, Pierangelo; Busso, Marco; Tinivella, Marco; Artusi, Carlo Alberto; De Mercanti, Stefania; Cucci, Angele; Veltri, Andrea; Avagnina, Paolo; Calvo, Andrea; Chio', Adriano; Durelli, Luca; Clerico, Marinella

2015-12-01

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2 ± 4.4 months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p < 0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6 ± 1 months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

Subcutaneous self-injections of C1 inhibitor: an effective and safe treatment in a patient with hereditary angio-oedema.

PubMed

Weller, K; Krüger, R; Maurer, M; Magerl, M

2016-01-01

A 25-year-old woman presented to our clinic with a history of recurrent swelling and abdominal symptoms for > 20 years. The patient's father was similarly affected. The patient was diagnosed with hereditary angio-oedema (HAE) due to C1 inhibitor deficiency. This was initially managed with systemic androgens, but the symptoms of hyperandrogenism eventually became intolerable. Treatment with icatibant (an antagonist of bradykinin B2 receptors) was partially successful. We changed the therapy to prophylactic treatment with C1 inhibitor. Although the patient became completely symptom-free under this regimen, she found the repeated intravenous injections unacceptable. Therefore, we changed the route of administration to subcutaneous injections of C1 inhibitor 1000 U in 10 mL twice weekly, using a subcutaneous infusion kit. Since that time (December 2013), she has remained completely free of symptoms under this regimen. To our knowledge, this is the first report documenting the efficacy and safety of subcutaneous injections of C1 inhibitor in a patient with HAE. © 2015 British Association of Dermatologists.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

PubMed

Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

2016-01-01

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

PubMed

Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

2016-04-01

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

Space nuclear power applied to electric propulsion

NASA Technical Reports Server (NTRS)

Vicente, F. A.; Karras, T.; Darooka, D.; Isenberg, L.

1989-01-01

Space reactor power systems with characteristics ideal for advanced spacecraft systems applications are discussed. These characteristics are: high power-to-weight ratio (15 to 33 W/kg); high volume density (high ballistic coefficient); no preferential orientation in orbit; long operational life; high reliability; and total launch and operational safety. These characteristics allow the use of electric propulsion to raise spacecraft from low earth parking orbits to operational orbits, greatly increasing the useful orbit payload for a given launch vehicle by eliminating the need for a separation injection stage. A proposed demonstration mission is described.

Scale Model Test and Transient Analysis of Steam Injector Driven Passive Core Injection System for Innovative-Simplified Nuclear Power Plant

NASA Astrophysics Data System (ADS)

Ohmori, Shuichi; Narabayashi, Tadashi; Mori, Michitsugu

A steam injector (SI) is a simple, compact and passive pump and also acts as a high-performance direct-contact compact heater. This provides SI with capability to serve also as a direct-contact feed-water heater that heats up feed-water by using extracted steam from turbine. Our technology development aims to significantly simplify equipment and reduce physical quantities by applying "high-efficiency SI", which are applicable to a wide range of operation regimes beyond the performance and applicable range of existing SIs and enables unprecedented multistage and parallel operation, to the low-pressure feed-water heaters and emergency core cooling system of nuclear power plants, as well as achieve high inherent safety to prevent severe accidents by keeping the core covered with water (a severe accident-free concept). This paper describes the results of the scale model test, and the transient analysis of SI-driven passive core injection system (PCIS).

WISE recommendations to ensure the safety of injections in diabetes.

PubMed

Strauss, K

2012-01-01

Injections and fingersticks administered to patients with diabetes in health care settings present a risk of blood exposure to the injector as well as other workers in potential contact with sharps. Such exposures could lead to transmission of bloodborne pathogens such as hepatitis and HIV. A recent EU Directive requires that where such risks have been identified, processes and devices must be put in place to reduce or eliminate the risk. The aim of this paper is to provide formal guidelines on the application of this Directive to diabetes care settings. These evidence-based recommendations were written and vetted by a large group of international safety experts. A systematic literature search was conducted for all peer-reviewed studies and publications which bear on sharps safety in diabetes. Initially a group of experts reviewed this literature and drafted the recommendations. These were then presented for review, debate and revision to 57 experts from 14 countries at the WISE workshop in October, 2011. After the WISE meeting, the revised Recommendations were circulated electronically to attendees on three occasions, each time in a new iteration with revisions. Each recommendation was graded by the weight it should have in daily practice and by its degree of support in the medical literature. The topics covered include Risks of Sharps Injury and Muco-cutaneous Exposure, The EU Directive, Device Implications, Injection Technique Implications, Education and Training (Creating a "Safety Culture"), Value, Awareness and Responsibility. These safety recommendations provide practical guidance and fill an important gap in diabetes management. If followed, they should help ensure safe, effective and largely injury-free injections and fingersticks. They will serve as the roadmap for applying the new EU Directive to diabetes care. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Clinical investigations of polymethylmethacrylate cement viscosity during vertebroplasty and related in vitro measurements

PubMed Central

Boger, A.; Schenk, B.; Heini, P. F.

2009-01-01

Percutaneous vertebroplasty, comprising an injection of polymethylmethacrylate (PMMA) into vertebral bodies, is a practical procedure for the stabilization of osteoporotic compression fractures as well as other weakening lesions. Cement leakage is considered to be one of the major and most severe complications during percutaneous vertebroplasty. The viscosity of the material plays a key role in this context. In order to enhance the safety for the patient, a rheometer system was developed to measure the cement viscosity intraoperatively. For this development, it is of great importance to know the proper viscosity to start the procedure determined by experienced surgeons and the relation between the time period when different injection devices are used and the cement viscosity. The purpose of the study was to investigate the viscosity ranges for different injection systems during conventional vertebroplasty. Clinically observed viscosity values and related time periods showed high scattering. In order to get a better understanding of the clinical observations, cement viscosity during hardening at different ambient temperatures and by simulation of the body temperature was investigated in vitro. It could be concluded, that the direct viscosity assessment with a rheometer during vertebroplasty can help clinicians to define a lower threshold viscosity and thereby decrease the risk of leakage and make adjustments to their injection technique in real time. Secondly, the acceleration in hardening of PMMA-based cements at body temperature can be useful in minimizing leakages by addressing them with a short injection break. PMID:19479285

A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety

PubMed Central

Wang, Ying; Wu, Ke-Chun; Zhao, Bing-Xiang; Zhao, Xin; Wang, Xin; Chen, Su; Nie, Shu-Fang; Pan, Wei-San; Zhang, Xuan; Zhang, Qiang

2011-01-01

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P < .01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy. PMID:21331356

[Efficacy and safety of Danhong injection for idiopathic pulmonary fibrosis：Meta-analysis].

PubMed

Xin, Li-Li; Jiang, Miao; Zhang, Geng; Gong, Jie-Ning

2016-10-01

To systematically review the efficacy and safety of Danhong injection for patients with idiopathic pulmonary fibrosis(IPF), two researchers electronically searched PubMed, EMbase, Web of Science, Cochrane Library, CNKI, CBM, WanFang Data and VIP databases from the date of establishment to May 2016 for all randomized controlled trials(RCTs) and quasi-RCTs on the use of Danhong injection in patients with IPF. Manual search in relevant journals and search of relevant literature on other websites were also performed. The data extraction and quality assessment of included RCTs and quasi-RCT were conducted by two reviewers independently. Then, Meta-analysis was conducted by using RevMan 5.3 software. A total of 12 RCTs involving 844 patients were included, 423 cases in experiment group and 421 cases in control group. The results of meta-analysis indicated that the Danhong injection group was superior than the control group in clinical effectiveness(RR=1.36, 95%CI 1.25 to 1.49, P<0.000 01), increased DLCO value(MD=4.25, 95%CI 3.32 to 5.18, P<0.000 01), and increased PaO2 value(MD=14.51, 95%CI 12.35 to 16.68, P<0.000 01). The analysis results showed that Danhong injection could significantly reduce the level of TGF-β1 in serum. There were no serious or frequently happened adverse effects in the Danhong injection group, indicating high safety and good tolerance of Danhong injection in treatment of IPF. The current evidences suggested that Danhong injection in short term use(<12 weeks) could increase clinical effectiveness, improve DLCO and PaO2, and decrease the level of TGF-β1 in serum of IPF patients, with less adverse effects. However, these results should be carefully interpreted due to the low methodology quality and small sample size of trials, and this conclusion had to be further verified by high quality, large scale and double blinded RCTs. Copyright© by the Chinese Pharmaceutical Association.

Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

PubMed Central

Chang, Ming-Fong; Hsieh, Jung-Hsien; Chiang, Hao; Kan, Hung-Wei; Huang, Cho-Min; Chellis, Luke; Lin, Bo-Shiou; Miaw, Shi-Chuen; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

2016-01-01

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection. PMID:27748450

Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials.

PubMed

Gaudinski, Martin R; Houser, Katherine V; Morabito, Kaitlyn M; Hu, Zonghui; Yamshchikov, Galina; Rothwell, Ro Shauna; Berkowitz, Nina; Mendoza, Floreliz; Saunders, Jamie G; Novik, Laura; Hendel, Cynthia S; Holman, LaSonji A; Gordon, Ingelise J; Cox, Josephine H; Edupuganti, Srilatha; McArthur, Monica A; Rouphael, Nadine G; Lyke, Kirsten E; Cummings, Ginny E; Sitar, Sandra; Bailer, Robert T; Foreman, Bryant M; Burgomaster, Katherine; Pelc, Rebecca S; Gordon, David N; DeMaso, Christina R; Dowd, Kimberly A; Laurencot, Carolyn; Schwartz, Richard M; Mascola, John R; Graham, Barney S; Pierson, Theodore C; Ledgerwood, Julie E; Chen, Grace L

2018-02-10

The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. VRC5283 was well tolerated and has advanced to phase 2 efficacy testing. Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Copyright © 2018 Elsevier Ltd. All rights reserved.

THE REAL ESTATE OF MYOBLAST CARDIAC TRANSPLANTATION – NEGATIVE REMODELING IS ASSOCIATED WITH LOCATION

PubMed Central

McCue, Jonathan D.; Swingen, Cory; Feldberg, Tanya; Caron, Gabe; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath; Motilall, Randy; Breviu, Brian; Taylor, Doris A.

2009-01-01

Background Skeletal myoblast (SKMB) transplantation has been proposed as a therapy for ischemic cardiomyopathy due to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that SKMB transplanted into peripheral scar (compared to central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. Methods 34 New Zealand White rabbits underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation SKMBs were injected either in the scar center (n=13) or scar periphery (n=10) and compared to saline injection (n=11). Holter monitoring and MRI was performed pre-injection; Holter monitoring was continued until two weeks post injection, with follow-up MRI at one month. Results Centrally-treated animals demonstrated increased LV end systolic volume, end diastolic volume and mass that correlated with injected cell number. There was a trend toward attenuation of negative LV remodeling in peripherally-treated animals compared to vehicle. Significant late ectopy was seen in several centrally-injected animals with no late ectopy seen in peripherally-injected animals. Conclusions We noted untoward effects with respect to negative LV remodeling following central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of SKMB cardiac transplantation. Administration of SKMBs into peripheral scar appears safe with a trend toward improved function in comparison to sham injection. PMID:18187097

Ultrasound-guided corticosteroid injection therapy for juvenile idiopathic arthritis: 12-year care experience.

PubMed

Young, Cody M; Shiels, William E; Coley, Brian D; Hogan, Mark J; Murakami, James W; Jones, Karla; Higgins, Gloria C; Rennebohm, Robert M

2012-12-01

Intra-articular corticosteroid injections are a safe and effective treatment for patients with juvenile idiopathic arthritis. The potential scope of care in ultrasound-guided corticosteroid therapy in children and a joint-based corticosteroid dose protocol designed to optimize interdisciplinary care are not found in the current literature. The purpose of this study was to report the spectrum of care, technique and safety of ultrasound-guided corticosteroid injection therapy in patients with juvenile idiopathic arthritis and to propose an age-weight-joint-based corticosteroid dose protocol. A retrospective analysis was performed of 198 patients (ages 21 months to 28 years) referred for treatment of juvenile idiopathic arthritis with corticosteroid therapy. Symptomatic joints and tendon sheaths were treated as prescribed by the referring rheumatologist. An age-weight-joint-based dose protocol was developed and utilized for corticosteroid dose prescription. A total of 1,444 corticosteroid injections (1,340 joints, 104 tendon sheaths) were performed under US guidance. Injection sites included small, medium and large appendicular skeletal joints (upper extremity 497, lower extremity 837) and six temporomandibular joints. For patients with recurrent symptoms, 414 repeat injections were performed, with an average time interval of 17.7 months (range, 0.5-101.5 months) between injections. Complications occurred in 2.6% of injections and included subcutaneous tissue atrophy, skin hypopigmentation, erythema and pruritis. US-guided corticosteroid injection therapy provides dynamic, precise and safe treatment of a broad spectrum of joints and tendon sheaths throughout the entire pediatric musculoskeletal system. An age-weight-joint-based corticosteroid dose protocol is effective and integral to interdisciplinary care of patients with juvenile idiopathic arthritis.

Demonstration of fully coupled simplified extended station black-out accident simulation with RELAP-7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Haihua; Zhang, Hongbin; Zou, Ling

2014-10-01

The RELAP-7 code is the next generation nuclear reactor system safety analysis code being developed at the Idaho National Laboratory (INL). The RELAP-7 code develop-ment effort started in October of 2011 and by the end of the second development year, a number of physical components with simplified two phase flow capability have been de-veloped to support the simplified boiling water reactor (BWR) extended station blackout (SBO) analyses. The demonstration case includes the major components for the primary system of a BWR, as well as the safety system components for the safety relief valve (SRV), the reactor core isolation cooling (RCIC)more » system, and the wet well. Three scenar-ios for the SBO simulations have been considered. Since RELAP-7 is not a severe acci-dent analysis code, the simulation stops when fuel clad temperature reaches damage point. Scenario I represents an extreme station blackout accident without any external cooling and cooling water injection. The system pressure is controlled by automatically releasing steam through SRVs. Scenario II includes the RCIC system but without SRV. The RCIC system is fully coupled with the reactor primary system and all the major components are dynamically simulated. The third scenario includes both the RCIC system and the SRV to provide a more realistic simulation. This paper will describe the major models and dis-cuss the results for the three scenarios. The RELAP-7 simulations for the three simplified SBO scenarios show the importance of dynamically simulating the SRVs, the RCIC sys-tem, and the wet well system to the reactor safety during extended SBO accidents.« less

System-level modeling for economic evaluation of geological CO2storage in gas reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yingqi; Oldenburg, Curtis M.; Finsterle, Stefan

2006-03-02

One way to reduce the effects of anthropogenic greenhousegases on climate is to inject carbon dioxide (CO2) from industrialsources into deep geological formations such as brine aquifers ordepleted oil or gas reservoirs. Research is being conducted to improveunderstanding of factors affecting particular aspects of geological CO2storage (such as storage performance, storage capacity, and health,safety and environmental (HSE) issues) as well as to lower the cost ofCO2 capture and related processes. However, there has been less emphasisto date on system-level analyses of geological CO2 storage that considergeological, economic, and environmental issues by linking detailedprocess models to representations of engineering components andassociatedmore » economic models. The objective of this study is to develop asystem-level model for geological CO2 storage, including CO2 capture andseparation, compression, pipeline transportation to the storage site, andCO2 injection. Within our system model we are incorporating detailedreservoir simulations of CO2 injection into a gas reservoir and relatedenhanced production of methane. Potential leakage and associatedenvironmental impacts are also considered. The platform for thesystem-level model is GoldSim [GoldSim User's Guide. GoldSim TechnologyGroup; 2006, http://www.goldsim.com]. The application of the system modelfocuses on evaluating the feasibility of carbon sequestration withenhanced gas recovery (CSEGR) in the Rio Vista region of California. Thereservoir simulations are performed using a special module of the TOUGH2simulator, EOS7C, for multicomponent gas mixtures of methane and CO2.Using a system-level modeling approach, the economic benefits of enhancedgas recovery can be directly weighed against the costs and benefits ofCO2 injection.« less

76 FR 20685 - Determination That NOVANTRONE (Mitoxantrone Hydrochloride) Injection, Equivalent to 25 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... that have been discontinued from marketing for reasons other than safety or effectiveness. FDA will not... Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... from sale for reasons of safety or effectiveness. This determination means that FDA will not begin...

77 FR 29665 - Determination That PITRESSIN TANNATE IN OIL (Vasopressin Tannate) Injection, 5 Pressor Units...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications... suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines...

77 FR 35985 - Determination That PARAPLATIN (Carboplatin) Injection and SUSTIVA (Efavirenz) Capsules Were Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice... document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that... the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the listed...

75 FR 24710 - Determination That BREVIBLOC (Esmolol Hydrochloride) Injection, 250 Milligrams/Milliliter, 10...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

..., Was Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration... from sale for reasons of safety or effectiveness. This determination means the agency will not accept... of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for...

77 FR 14810 - Determination That DURANEST (Etidocaine Hydrochloride) Injection, 0.5%, and Five Other DURANEST...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... marketing for reasons other than safety or effectiveness. ANDAs that refer to any of the DURANEST drug... Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug... reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug...

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

PubMed

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-10-06

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data.

PubMed

Cicero, Arrigo F G; Tartagni, Elisa; Ertek, Sibel

2014-08-01

To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treated patients at high risk for cardiovascular disease, new injectable lipid-lowering drugs with innovative mechanisms of action are in advanced phase of development or have just been approved. Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation. Mipomersen specifically binds to a segment of the human apolipoprotein B100 messenger RNA, blocking the translation of the gene product. Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. Mipomersen use is mainly associated to hepatosteatosis, increased transaminases (> 3 times the upper limit of normal), mild-to-moderate injection-site reactions and flu-like symptoms. PCSK9 inhibitors have demonstrated their good safety and tolerability in a large number of subjects with different clinical conditions, including statin-intolerance, enlarging their potential use in a broader range of patients. Further data on long-term mipomersen safety are required.

MODFLOW 2.0: A program for predicting moderator flow patterns

NASA Astrophysics Data System (ADS)

Peterson, P. F.; Paik, I. K.

1991-07-01

Sudden changes in the temperature of flowing liquids can result in transient buoyancy forces which strongly impact the flow hydrodynamics via flow stratification. These effects have been studied for the case of potential flow of stratified liquids to line sinks, but not for moderator flow in SRS reactors. Standard codes, such as TRAC and COMMIX, do not have the capability to capture the stratification effect, due to strong numerical diffusion which smears away the hot/cold fluid interface. A related problem with standard codes is the inability to track plumes injected into the liquid flow, again due to numerical diffusion. The combined effects of buoyant stratification and plume dispersion have been identified as being important in the operation of the Supplementary Safety System which injects neutron-poison ink into SRS reactors to provide safe shutdown in the event of safety rod failure. The MODFLOW code discussed here provides transient moderator flow pattern information with stratification effects, and tracks the location of ink plumes in the reactor. The code, written in Fortran, is compiled for Macintosh II computers, and includes subroutines for interactive control and graphical output. Removing the graphics capabilities, the code can also be compiled on other computers. With graphics, in addition to the capability to perform safety related computations, MODFLOW also provides an easy tool for becoming familiar with flow distributions in SRS reactors.

Hybrid propulsion technology program: Phase 1, volume 4

NASA Technical Reports Server (NTRS)

Claflin, S. E.; Beckman, A. W.

1989-01-01

The use of a liquid oxidizer-solid fuel hybrid propellant combination in booster rocket motors appears extremely attractive due to the integration of the best features of liquid and solid propulsion systems. The hybrid rocket combines the high performance, clean exhaust, and safety of liquid propellant engines with the low cost and simplicity of solid propellant motors. Additionally, the hybrid rocket has unique advantages such as an inert fuel grain and a relative insensitivity to fuel grain and oxidizer injection anomalies. The advantages mark the hybrid rocket as a potential replacement or alternative for current and future solid propellant booster systems. The issues are addressed and recommendations are made concerning oxidizer feed systems, injectors, and ignition systems as related to hybrid rocket propulsion. Early in the program a baseline hybrid configuration was established in which liquid oxygen would be injected through ports in a solid fuel whose composition is based on hydroxyl terminated polybutadiene (HTPB). Liquid oxygen remained the recommended oxidizer and thus all of the injector concepts which were evaluated assumed only liquid would be used as the oxidizer.

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

PubMed

Burke, Erin E; Zager, Jonathan S

2018-04-01

Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

Assurance Cases for Medical Devices

DTIC Science & Technology

2011-04-28

the patient, and the hospital setting. Some pumps allow the patient to control part of the injection process (e.g. to inject more painkiller ...overdose, incorrect therapy, etc.   Design and development decisions that bear on safety and effectiveness http://www.fda.gov/MedicalDevices

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model

PubMed Central

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. PMID:26968036

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

PubMed

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy.

Toxicology study for magnetic injection of prednisolone into the rat cochlea.

PubMed

Shimoji, M; Ramaswamy, B; Shukoor, M I; Benhal, P; Broda, A; Kulkarni, S; Malik, P; McCaffrey, B; Lafond, J-F; Nacev, A; Weinberg, I N; Shapiro, B; Depireux, D A

2018-06-19

This paper investigates the safety of a novel 'magnetic injection' method of delivering therapy to the cochlea, in a rodent model. In this method of administration, a magnetic field is employed to actively transport drug-eluting iron oxide-core nanoparticles into the cochlea, where they then release their drug payload (we delivered the steroid prednisolone). Our study design and selection of control groups was based on published regulatory guidance for safety studies that involve local drug delivery. We tested for both single and multiple delivery doses to the cochlea, and found that magnetic delivery did not harm hearing. There was no statistical difference in hearing between magnetically treated ears versus ears that received intra-tympanic steroid (a mimic of a standard-of-care for sudden sensorineural hearing loss), both 2 and 30 days after treatment. Since our treatment is local to the ear, the levels of steroid and iron circulating systemically after our treatment were low, below mass-spectrometry detection limits for the steroid and no different from normal for iron. No adverse findings were observed in ear tissue histopathology or in animal gross behavior. At 2 and 30 days after treatment, inflammatory changes in the ear were limited to the middle ear, were very mild in severity, and by day 90 there was ongoing and almost complete reversibility of these changes. There were no ear tissue scarring or hemorrhage trends associated with magnetic delivery. In summary, after conducting a pre-clinical safety study based on FDA guidance documents, no adverse safety issues were observed. Copyright © 2017. Published by Elsevier B.V.

Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles

PubMed Central

Kim, Yoo C.; Edelhauser, Henry F.; Prausnitz, Mark R.

2014-01-01

Purpose. In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body. Methods. A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3–6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α2-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared. Results. Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar. Conclusions. This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery. PMID:25212782

Understanding and managing the effects of battery charger and inverter aging

NASA Astrophysics Data System (ADS)

Gunther, W.; Aggarwal, S.

An aging assessment of battery chargers and inverters was conducted under the auspices of the NRC's Nuclear Plant Aging Research (NPAR) Program. The intentions of this program are to resolve issues related to the aging and service wear of equipment and systems at operating reactor facilities and to assess their impact on safety. Inverters and battery chargers are used in nuclear power plants to perform significant functions related to plant safety and availability. The specific impact of a battery charger or inverter failure varies with plant configuration. Operating experience data have demonstrated that reactor trips, safety injection system actuations, and inoperable emergency core cooling systems have resulted from inverter failures; and dc bus degradation leading to diesel generator inoperability or loss of control room annunication and indication have resulted from battery and battery charger failures. For the battery charger and inverter, the aging and service wear of subcomponents have contributed significantly to equipment failures. This paper summarizes the data and then describes methods that can be used to detect battery charger and inverter degradation prior to failure, as well as methods to minimize the failure effects. In both cases, the managing of battery charger and inverter aging is emphasized.

A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3).

PubMed

Alvarez, Ronald D; Huh, Warner K; Bae, Sejong; Lamb, Lawrence S; Conner, Michael G; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A; Hester, Shirley; Jackson, Bradford E; Wu, T C; Trimble, Cornelia L

2016-02-01

The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

A Pilot Study of pNGVL4a-CRT/E7(detox) for the Treatment of Patients with HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

PubMed Central

Alvarez, Ronald D.; Huh, Warner K.; Bae, Sejong; Lamb, Lawrence S.; Conner, Michael G.; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A.; Hester, Shirley; Jackson, Bradford E.; Wu, T.C.; Trimble, Cornelia

2015-01-01

Objective The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Methods Eligible patients with HPV16+ CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Results Thirty-two patients with HPV16+ CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. Conclusion pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. PMID:26616223

Experimental investigation of the impulse gas injection into liquid and the use of experimental data for verification of the HYDRA-IBRAE/LM thermohydraulic code

NASA Astrophysics Data System (ADS)

Lobanov, P. D.; Usov, E. V.; Butov, A. A.; Pribaturin, N. A.; Mosunova, N. A.; Strizhov, V. F.; Chukhno, V. I.; Kutlimetov, A. E.

2017-10-01

Experiments with impulse gas injection into model coolants, such as water or the Rose alloy, performed at the Novosibirsk Branch of the Nuclear Safety Institute, Russian Academy of Sciences, are described. The test facility and the experimental conditions are presented in details. The dependence of coolant pressure on the injected gas flow and the time of injection was determined. The purpose of these experiments was to verify the physical models of thermohydraulic codes for calculation of the processes that could occur during the rupture of tubes of a steam generator with heavy liquid metal coolant or during fuel rod failure in water-cooled reactors. The experimental results were used for verification of the HYDRA-IBRAE/LM system thermohydraulic code developed at the Nuclear Safety Institute, Russian Academy of Sciences. The models of gas bubble transportation in a vertical channel that are used in the code are described in detail. A two-phase flow pattern diagram and correlations for prediction of friction of bubbles and slugs as they float up in a vertical channel and of two-phase flow friction factor are presented. Based on the results of simulation of these experiments using the HYDRA-IBRAE/LM code, the arithmetic mean error in predicted pressures was calculated, and the predictions were analyzed considering the uncertainty in the input data, geometry of the test facility, and the error of the empirical correlation. The analysis revealed major factors having a considerable effect on the predictions. The recommendations are given on updating of the experimental results and improvement of the models used in the thermohydraulic code.

Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™.

PubMed

Vescovo, Paul; Rettby, Nils; Ramaniraka, Nirinarilala; Liberman, Julie; Hart, Karen; Cachemaille, Astrid; Piveteau, Laurent-Dominique; Zanoni, Reto; Bart, Pierre-Alexandre; Pantaleo, Giuseppe

2017-03-27

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Post-licensure surveillance of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ⩾19years old in the United States, Vaccine Adverse Event Reporting System (VAERS), June 1, 2012-December 31, 2015.

PubMed

Haber, Penina; Arana, Jorge; Pilishvili, Tamara; Lewis, Paige; Moro, Pedro L; Cano, Maria

2016-12-07

The 13-valent pneumococcal conjugate vaccine (PCV13) was first recommended for use in adults aged ⩾19years with immunocompromising conditions in June 2012. On August 2014, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of PCV13 among adults aged ⩾65years. We assessed adverse events (AEs) reports following PCV13 in adults aged ⩾19years reported to the Vaccine Adverse Event Reporting System (VAERS) from June 2012 to December 2015. VAERS is a national spontaneous reporting system for monitoring AEs following vaccination. Our assessment included automated data analysis, clinical review of all serious reports and reports of special interest. We conducted empirical Bayesian data mining to assess for disproportionate reporting. VAERS received 2976 US PCV13 adult reports; 2103 (71%) of these reports were from PCV13 administered alone. Fourteen percent were in persons aged 19-64years and 86% were in persons aged ⩾65years. Injection site erythema (28%), injection site pain (24%) and fever (22%) were the most frequent AEs among persons aged 19-64years; injection site erythema (30%), erythema (20%) and injection site swelling (18%) were the most frequent among persons aged ⩾65years who were given the vaccine alone. The most frequently reported AEs among non-death serious reports were injection site reactions and general malaise among persons 19-64years old; injection site reactions, general malaise and Guillain-Barré syndrome among those ⩾65years (Table 2). Data mining did not detect disproportional reporting for any unexpected AE. The results of this study were consistent with safety data from pre-licensure studies of PCV13. We did not detect any new or unexpected AEs. Published by Elsevier Ltd.

Design, Development, and Testing of a UAV Hardware-in-the-Loop Testbed for Aviation and Airspace Prognostics Research

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan; Teubert, Chris; Gorospe, George; Burgett, Drew; Quach, Cuong C.; Hogge, Edward

2016-01-01

The airspace is becoming more and more complicated, and will continue to do so in the future with the integration of Unmanned Aerial Vehicles (UAVs), autonomy, spacecraft, other forms of aviation technology into the airspace. The new technology and complexity increases the importance and difficulty of safety assurance. Additionally, testing new technologies on complex aviation systems & systems of systems can be very difficult, expensive, and sometimes unsafe in real life scenarios. Prognostic methodology provides an estimate of the health and risks of a component, vehicle, or airspace and knowledge of how that will change over time. That measure is especially useful in safety determination, mission planning, and maintenance scheduling. The developed testbed will be used to validate prediction algorithms for the real-time safety monitoring of the National Airspace System (NAS) and the prediction of unsafe events. The framework injects flight related anomalies related to ground systems, routing, airport congestion, etc. to test and verify algorithms for NAS safety. In our research work, we develop a live, distributed, hardware-in-the-loop testbed for aviation and airspace prognostics along with exploring further research possibilities to verify and validate future algorithms for NAS safety. The testbed integrates virtual aircraft using the X-Plane simulator and X-PlaneConnect toolbox, UAVs using onboard sensors and cellular communications, and hardware in the loop components. In addition, the testbed includes an additional research framework to support and simplify future research activities. It enables safe, accurate, and inexpensive experimentation and research into airspace and vehicle prognosis that would not have been possible otherwise. This paper describes the design, development, and testing of this system. Software reliability, safety and latency are some of the critical design considerations in development of the testbed. Integration of HITL elements in the development phases and veri cation/ validation are key elements to this report.

Comparison of the EZ-Cap recapper with the Mayo recapper for the prevention of needlesticks.

PubMed

Dewhirst, Chad A; Hung, Joseph C

2008-09-01

The purpose of this project was the development of a device that improves the design of our current capping block, the Mayo recapper. The major challenges for design and improvement included creating a device that is simple to use and can be applied throughout our department. We wanted a recapper device that increased safety and minimized the potential for needlesticks. Simplicity was another important factor, along with versatility and low cost. A new recapper, called EZ-Cap, was developed, and a comparison study was conducted to evaluate the pros and cons of the EZ-Cap recapper and the Mayo recapper. Nuclear medicine technologists (n = 10) in our department used each device when administering patient injections. At the conclusion of their patient injection rotation, they recorded on a survey sheet the pros and cons of each device. The results of this survey were used to evaluate the effectiveness, comfort level during use, and safety of each recapping device. We used a 2-level scoring system to help determine which device was more favorable. The first level focused on comfort and convenience and was given a score of +1 or -1. The second level focused on safety and was given a score of +2 or -2. Because we believed that safety was a high priority for our capping blocks, this level received a higher score than the first level. The Mayo recapper was the device preferred by 9 of 10 technologists surveyed. The EZ-Cap recapper had several technical issues that made it difficult to use and that could potentially lead to safety concerns. According to our scoring system, the Mayo recapper received a score of +9 for its pros and -4 for its cons. By comparison, the EZ-Cap recapper received a score of +7 for its pros and -16 for its cons. Our results show that the Mayo recapper was the device of choice because its pros outweighed its cons. However, we will continually improve the effectiveness of the Mayo recapper to prevent needlesticks.

Surgeon Training in Telerobotic Surgery via a Hardware-in-the-Loop Simulator

PubMed Central

Alemzadeh, Homa; Chen, Daniel; Kalbarczyk, Zbigniew; Iyer, Ravishankar K.; Kesavadas, Thenkurussi

2017-01-01

This work presents a software and hardware framework for a telerobotic surgery safety and motor skill training simulator. The aims are at providing trainees a comprehensive simulator for acquiring essential skills to perform telerobotic surgery. Existing commercial robotic surgery simulators lack features for safety training and optimal motion planning, which are critical factors in ensuring patient safety and efficiency in operation. In this work, we propose a hardware-in-the-loop simulator directly introducing these two features. The proposed simulator is built upon the Raven-II™ open source surgical robot, integrated with a physics engine and a safety hazard injection engine. Also, a Fast Marching Tree-based motion planning algorithm is used to help trainee learn the optimal instrument motion patterns. The main contributions of this work are (1) reproducing safety hazards events, related to da Vinci™ system, reported to the FDA MAUDE database, with a novel haptic feedback strategy to provide feedback to the operator when the underlying dynamics differ from the real robot's states so that the operator will be aware and can mitigate the negative impact of the safety-critical events, and (2) using motion planner to generate semioptimal path in an interactive robotic surgery training environment. PMID:29065635

Botulinum Toxin Injections: A Treatment for Muscle Spasms

MedlinePlus

... Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family Health Infants and ... Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control ...

Physicochemical characterization and an injection formulation study of water insoluble ZCVI₄-2, a novel NO-donor anticancer compound.

PubMed

Gao, Yuan; Li, Li; Zhang, Jianjun; Su, Feng; Gong, Zhenhua; Lai, Yisheng; Zhang, Yihua

2012-07-01

ZCVI(4)-2 was a novel nitric oxide-releasing glycosyl derivative of oleanolic acid that displayed strong cytotoxicity selectively against human hepatocellular carcinoma in vitro and in vivo. In this study, ZCVI(4)-2 was characterized by FT-IR spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, Raman spectroscopy, hygroscopicity and stability. A high performance liquid chromatography method was also established for the quantitative determination of solubility and additional stability profile of ZCVI(4)-2. ZCVI(4)-2 was found to be an amorphous and stable solid with low solubility of less than 10 μg/mL. Based on the solubilization tests that included methods of cosolvency and micellization, the solution mixture of 5% Solutol HS-15, 5% 1, 2-propylene glycol and 5% anhydrous ethanol was determined to be the system for the preparation of the ZCVI(4)-2 early injection solution. The effect of pH, temperature, light and injectable isotonic glucose or NaCl solution on ZCVI(4)-2 injection was also investigated. Good stability was observed at all testing conditions. Under the conditions studied, the NO-releasing rate and amount of ZCVI(4)-2 from the early injection solution in rat plasma demonstrated a promising therapeutic efficacy while maintaining a good safety profile.

Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China.

PubMed

He, L; Wen, J; Jiang, X; Chen, H; Tang, Y

2011-06-01

The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application. © 2011 Blackwell Verlag GmbH.

Evolution of the central safety factor during stabilized sawtooth instabilities at KSTAR

NASA Astrophysics Data System (ADS)

Messmer, M. C. C.; Ko, J.; Chung, J.; Woo, M. H.; Lee, K.-D.; Jaspers, R. J. E.

2018-01-01

A motional Stark effect (MSE) diagnostic has recently been installed in the KSTAR tokamak. A difficulty faced at KSTAR and common to other MSE diagnostics is calibration of the system for absolute measurements. In this report we present our novel calibration routine and discuss first results, evaluating the evolution of the the central safety factor during sawtooth instabilities. The calibration scheme ensures that the bandpass filters typically used in MSE systems are aligned correctly and identifies and removes systematic offsets present in the measurement. This is verified by comparing the reconstructed safety factor profile against various discharges where the locations of rational q surfaces have been obtained from MHD markers. The calibration is applied to analyse the evolution of q 0 in a shot where the sawteeth are stabilized by neutral beam injection. Within the analysed sawtooth periods q 0 drops below unity during the quiescent phase and relaxes close to or slightly above unity at the sawtooth crash. This finding is in line with the classical Kadomtsev model of full magnetic reconnection and earlier findings at JET.

Mechanism and Safety at the Threshold of the Blood-Brain Barrier Opening In Vivo

NASA Astrophysics Data System (ADS)

Konofagou, Elisa E.; Choi, James; Baseri, Babak; Selert, Kirsten; Tung, Yao-Sheng

2010-03-01

Current treatments of neurological and neurodegenerative diseases are limited due to the blood-brain barrier (BBB). In this paper, the threshold of BBB opening and its dependence on the microbubble diameter as well as the associated mechanism and safety are identified in vivo. In vivo BBB opening in mice (n = 13) was achieved by systemically injecting microbubbles (Definity and 1-2 and 4-5-μm lipid-shelled, gas-filled) and applying pulsed FUS (frequency: 1.525 MHz, peak-rarefactional pressure: 150-600 kPa) to the left hippocampus through the intact skin and skull. Systemically administered, BBB-impermeable, fluorescent-tagged dextrans at 3 kDa were injected to confirm BBB opening. H&E histology was also performed to determine any associated vascular or neuronal damage. Detection of stable and inertial cavitation was performed using a passive cavitation device (PCD) in a blood vessel phantom at the same pressure amplitudes as those used in vivo. Larger microbubbles (4-5 μm) resulted in a lower threshold of BBB opening. Cavitation studies confirmed that stable cavitation occurs at the threshold of BBB opening. The mechanism of BBB opening at the threshold was identified to be mainly related to stable cavitation. Histological studies indicated that, at the BBB opening threshold, no red-blood cell extravasation or neuronal damage was noted.

Nonclinical Safety Assessment of Anti-Factor D: Key Strategies and Challenges for the Nonclinical Development of Intravitreal Biologics.

PubMed

Bantseev, Vladimir; Erickson, Rebecca; Leipold, Douglas; Amaya, Caroline; Miller, Paul E; Booler, Helen; Thackaberry, Evan A

The nonclinical toxicology program described here was designed to characterize the safety profile of anti-factor D (AFD; FCFD4514S, lampalizumab) to support intravitreal (ITV) administration in patients with geographic atrophy (GA). The toxicity of AFD was assessed in a single-dose and 6-month repeat-dose study in monkeys at doses up to 10 mg/eye. Toxicity was assessed by clinical ophthalmic examinations, intraocular pressure measurements, ocular photography, electroretinography, fluorescein angiography, optical coherence tomography, and anatomic pathology. Systemic exposure to AFD generally increased with the increase in dose level. The increases in mean maximal concentration and area under the curve values were roughly dose proportional. No accumulation of AFD was observed following 10 doses, and drug exposures were not affected by anti-drug antibodies. AFD was locally and systemically well tolerated in monkeys following ITV doses of up to 10 mg/eye. Ocular effects associated with AFD were limited to transient, reversible, dose-related, aqueous cell responses and injection-related, mild, vitreal cell responses. In the 6-month repeat-dose study, 2 monkeys had a nonspecific immune response to AFD that resulted in severe ocular inflammation, attributed to administration of a heterologous (humanized) protein. The comprehensive toxicology program in monkeys described here was designed to evaluate the safety profile of AFD and to support multiple ITV injections in the clinic. Administration of a heterologous (humanized) protein presents a challenge, and immunogenicity in nonclinical species is not predictive of immunogenicity in humans. Taken together, the results of the nonclinical program described here support the use of AFD in patients with GA.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

PubMed

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

The real estate of myoblast cardiac transplantation: negative remodeling is associated with location.

PubMed

McCue, Jonathan D; Swingen, Cory; Feldberg, Tanya; Caron, Gabe; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath; Motilall, Randy; Breviu, Brian; Taylor, Doris A

2008-01-01

Skeletal myoblast transplantation has been proposed as a therapy for ischemic cardiomyopathy owing to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that skeletal myoblasts transplanted into peripheral scar (compared with central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. New Zealand White rabbits (n = 34) underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation, skeletal myoblasts were injected either in the scar center (n = 13) or scar periphery (n = 10) and compared with saline injection (n = 11). Holter monitoring and magnetic resonance imaging (MRI) was performed pre-injection; Holter monitoring was continued until 2 weeks after injection, with follow-up MRI at 1 month. The centrally treated animals demonstrated increased LV end-systolic volume, end-diastolic volume, and mass that correlated with the number of injected cells. There was a trend toward attenuation of negative LV remodeling in peripherally treated animals compared with vehicle. Significant late ectopy was seen in several centrally injected animals, with no late ectopy seen in peripherally injected animals. We noted untoward effects with respect to negative LV remodeling after central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of skeletal myoblast cardiac transplantation. Administration of skeletal myoblasts into peripheral scar appears safe, with a trend toward improved function in comparison with sham injection.

Huangqi injection (a traditional Chinese patent medicine) for chronic heart failure: a systematic review.

PubMed

Fu, Shufei; Zhang, Junhua; Menniti-Ippolito, Francesca; Gao, Xiumei; Galeotti, Francesca; Massari, Marco; Hu, Limin; Zhang, Boli; Ferrelli, Rita; Fauci, Alice; Firenzuoli, Fabio; Shang, Hongcai; Guerra, Ranieri; Raschetti, Roberto

2011-05-06

Chronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL). To evaluate the efficacy and safety of Huangqi injection for CHF according to the available scientific knowledge. An extensive search including PubMed, EMBASE, CBM, the Cochrane Library and Chinese literature databases was performed up to July 2008. Clinical trials regarding Huangqi injection for the treatment of CHF were searched for, irrespective of languages. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration and STATA 9.2 were used for data analysis. After selection of 1,205 articles, 62 RCTs and quasi-RCTs conducted in China and published in Chinese journals were included in the review. The methodological quality of the trials was low. In most trials inclusion and exclusion criteria were not specified. Furthermore, only one study evaluated the outcomes for drug efficacy after an adequate period of time. For these reasons and because of the different baseline characteristics we did not conduct a meta-analysis. Although available studies are not adequate to draw a conclusion on the efficacy and safety of Huangqi injection (a traditional Chinese patent medicine), we hope that our work could provide useful experience on further studies on Huangqi injections. The overall level of TCM clinical research needs to be improved so that the efficacy of TCM can be evaluated by the international community and possibly some TCM can enter into the international market.

Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up.

PubMed

Rodrigo, Sander F; van Ramshorst, Jan; Hoogslag, Georgette E; Boden, Helèn; Velders, Matthijs A; Cannegieter, Suzanne C; Roelofs, Helene; Al Younis, Imad; Dibbets-Schneider, Petra; Fibbe, Willem E; Zwaginga, Jaap Jan; Bax, Jeroen J; Schalij, Martin J; Beeres, Saskia L; Atsma, Douwe E

2013-10-01

In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P = 0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.

Preclinical Biodistribution and Safety Evaluation of a pbi-shRNA STMN1 Lipoplex after Subcutaneous Delivery.

PubMed

Wang, Zhaohui; Jay, Christopher M; Evans, Courtney; Kumar, Padmasini; Phalon, Connor; Rao, Donald D; Senzer, Neil; Nemunaitis, John

2017-02-01

Stathmin-1 (STMN1) is a microtubule-destabilizing protein which is overexpressed in cancer. Its overexpression is associated with poor prognosis and also serves as a predictive marker to taxane therapy. We have developed a proprietary bi-functional shRNA (bi-shRNA) platform to execute RNA interference (RNAi)-mediated gene silencing and a liposome-carrier complex to systemically deliver the pbi-shRNA plasmids. In vitro and in vivo testing demonstrated efficacy and specificity of pbi-shRNA plasmid in targeting STMN1 (Phadke, A. P., Jay, C. M., Wang, Z., Chen, S., Liu, S., Haddock, C., Kumar, P., Pappen, B. O., Rao, D. D., Templeton, N. S., et al. (2011). In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human Stathmin 1 oncoprotein. DNA Cell Biol. 30, 715-726.). Biodistribution and toxicology studies in bio-relevant Sprague Dawley rats with pbi-shRNA STMN1 lipoplex revealed that the plasmid DNA was delivered to a broad distribution of organs after a single subcutaneous injection. Specifically, plasmid was detected within the first week using QPCR (threshold 50 copies plasmid/1 µg genomic DNA) at the injection site, lung, spleen, blood, skin, ovary (limited), lymph nodes, and liver. It was not detected in the heart, testis or bone marrow. No plasmid was detected from any organ 30 days after injection. Treatment was well tolerated. Minimal inflammation/erythema was observed at the injection site. Circulating cytokine response was also examined by ELISA. The IL-6 levels were induced within 6 h then declined to the vehicle control level 72 h after the injection. TNFα induction was transiently observed 4 days after the DNA lipoplex treatment. In summary, the pbi-shRNA STMN1 lipoplex was well tolerated and displayed broad distribution after a single subcutaneous injection. The pre-clinical data has been filed to FDA and the pbi-shRNA STMN1 lipoplex is being investigated in a phase I clinical study. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Efficacy and Safety of Autologous Stromal Vascular Fraction in the Treatment of Empty Nose Syndrome.

PubMed

Kim, Do-Youn; Hong, Hye Ran; Choi, Eun Wook; Yoon, Sang Won; Jang, Yong Ju

2018-05-16

Regenerative treatment using stem cells may serve as treatment option for empty nose syndrome (ENS), which is caused by the lack of turbinate tissue and deranged nervous system in the nasal cavity. We aimed to assess the efficacy and safety of the autologous stromal vascular fraction (SVF) in the treatment of ENS. In this prospective observational clinical study, we enrolled 10 ENS patients who volunteered to undergo treatment of ENS through the injection of autologous SVF. Data, including demographic data, pre- and postoperative Sino-Nasal Outcome Test-25 (SNOT-25) scores, overall patient satisfaction, and postoperative complications, were prospectively collected. Nasal secretion was assessed using the polyurethane foam absorption method, and the levels of biological markers were analyzed in both ENS group and control group using enzyme-linked immunosorbent assay. The SVF extracted from abdominal fat was diluted and injected into both inferior turbinates. Among the 10 initial patients, one was excluded from the study. Subjective satisfaction was rated as "much improved" in two and "no change" in seven. Among the improved patients, the mean preinjection SNOT-25 score was 55.0 and the score at 6 months after injection was 19.5. However, the average SNOT-25 score of nine participants at 6 months after injection (mean±standard deviation, 62.4±35.8) did not differ significantly from the baseline SNOT25 score (70.1±24.7, P>0.05, respectively). Among the various inflammatory markers assessed, the levels of interleukin (IL)-1β, IL-8, and calcitonin gene-related peptide were significantly higher in ENS patients. Compared with preinjection secretion level, the nasal secretions from SVF-treated patients showed decreased expressions of IL-1β and IL-8 after injection. Although SVF treatment appears to decrease the inflammatory cytokine levels in the nasal mucosa, a single SVF injection was not effective in terms of symptom improvement and patient satisfaction. Further trials are needed to identify a more practical and useful regenerative treatment modality for patients with ENS.

Harnessing Neuroplasticity to Promote Rehabilitation: CI Therapy for TBI

DTIC Science & Technology

2015-10-01

Efficacy, and Pharmacokinetics of SAGE- 547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus (Szaflarski, PI...objective is to evaluate the safety and tolerability of SAGE-547 Injection (SAGE-547) in subjects in super-refractory status epilepticus (SRSE) This is a

Utility interface issues for grid-connected photovoltaic systems

NASA Astrophysics Data System (ADS)

Chu, D.; Key, T.; Fitzer, J.

Photovoltaic (PV) balance-of-system research and development has focused on interconnection with the utility grid as the most promising future application for photovoltaic energy production. These sysems must be compatible with the existing utility grid to be accepted. Compatibility encompasses many technical, economic and institutional issues, from lineman safety to revenue metering and power quality. This paper reviews DOE/PV sponsored research for two of the technical interconnection issues: harmonic injection, and power factor control. Explanations and rationale behind these two issues will be reviewed, and the status of current research and plans for required future work will be presented.

Critical appraisal of 3-monthly paliperidone depot injections in the treatment of schizophrenia.

PubMed

Carpiniello, Bernardo; Pinna, Federica

2016-01-01

Three-monthly injections of paliperidone palmitate (PP-3M) represent a new and recently introduced long-acting antipsychotic therapeutic option. This review focuses on available data relating to the efficacy and safety of PP-3M and its position in the current therapeutic scenario. An analysis of PubMed, Scopus, and ISI Web of Knowledge databases was conducted, and all available papers on PP-3M, including poster presentations, were selected and considered for the purpose of the present review. to date, three full papers have been published, the first, a Phase 1 randomized, open label study investigating the pharmacokinetics, safety, and tolerability of the drug; the second, a Phase 3 double blind study vs placebo focusing on efficacy and tolerability; and the last relating to the practical use of PP-3M. The five posters identified describe data reported in the above-cited papers. Overall, the pharmacokinetic findings obtained in these studies highlight the feasibility of administering PP-3M on a 3-monthly basis, subsequent to the administration of four 1-monthly injections of PP at doses 3.5 times higher than the stabilized dose of 1-monthly injections of PP (ie, 175, 300, 450, and 525 mgs). The published studies highlight a significantly longer time to relapse compared to placebo, and significantly better results compared to placebo for all secondary end-points (Positive and Negative Syndrome Scale, Clinical Global Impression-Severity Scale, Personal and Social Performance Scale scores), in addition to reasonably good safety and tolerability profiles. PP-3M emerges as a potential candidate for use as a first-line long-acting agent in the maintenance treatment of patients with schizophrenia. Further studies should however be conducted to confirm this expectation. In view of its efficacy, tolerability, and safety, together with the longer timespan between injections, PP-3M currently represents one of the best available options, and may contribute towards addressing the issue of poor adherence, even in early psychosis.

Old and new adjuvants for hepatitis B vaccines.

PubMed

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

New Reconstruction Technologies Of Safety Pillar In Mines / Nowoczesne Technologie Odbudowy Filara Bezpieczeństwa w Kopalniach

NASA Astrophysics Data System (ADS)

Gonet, Andrzej; Stryczek, Stanisław; Brudnik, Krzysztof

2012-11-01

Safety pillars are made around mines as a protection measure. This is especially important in salt mines where the surrounding waters are most hazardous. Without maintaining safe conditions the mine may be water-flooded as it was the case in one of the Polish mine "Wapno". An original technology linking pipeline injection and hole injection methods has been used for the reconstruction of a safety pillar in the Salt Mine "Wieliczka". This solution turned out to be successful when on 13 April 1992 the mine was saved from flooding after a disastrous water flux to the transverse working Mina. The presented technology can be efficiently used in various mines at the stage of designing, though their exploitation to the closing stage.

Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein.

PubMed

Du, Wei-Xin; Chen, Bao-Wen; Lu, Jin-Biao; Gao, Meng-Qiu; Shen, Xiao-Bing; Yang, Lei; Su, Cheng; Wang, Guo-Zhi; Sun, Qing-feng; Xu, Miao

2013-05-15

To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in preclinical and phase I clinical study. Guinea pigs were sensitized with different Mycobacteria. After sensitization, all animals were intradermally injected with rESAT6 and either PPD or PPD-B. At 24 h after the injection, the erythema of the injection sites were measured using a double-blind method. For the preclinical safety study, different doses of rESAT6 and BSA were given 3 times intramuscularly to guinea pigs. On day 14 after the final immunization, the guinea pigs were intravenously injected with the same reagents in the hind legs and the allergic reactions were observed. A single-center, randomized, open phase I clinical trial was employed. The skin test was conducted in 32 healthy volunteers aged 19-65 years with 0.1 µg, 0.5 µg, and 1 µg rESAT6. Physical examination and laboratory tests were performed before and after the skin test and adverse reactions were monitored. The volunteers' local and systemic adverse reactions and adverse events were recorded for 7 days. Positive PPD or PPD-B skin tests were observed in all Mycobacteria-sensitized guinea pigs; the diameters of erythema were all >10 mm. The rESAT6 protein induced a positive skin test result in the guinea pigs sensitized with MTB, M. bovis, M. africanum and M. kansasii; the diameters of erythema were 14.7±2.0, 9.3±3.8, 18.7±2.4, and 14.8±4.2 mm, respectively. A negative skin test result was detected in BCG-vaccinated and other NTM-sensitized guinea pigs. The rESAT6 caused no allergic symptoms, but many allergic reactions, such as cough, dyspnea, and even death, were observed in the guinea pigs who were administered BSA. During the phase I clinical trial, no adverse reactions were found in the 0.1 µg rESAT6 group, but in the 0.5 µg rESAT6 group 2 volunteers reported pain and 1 reported itching, and in the 1 µg rESAT6 group there was 1 case of pain, 1 case of itching, and 1 case of blister. No other local or systemic adverse reactions or events were reported. The rESAT6 can differentiate effectively among MTB infection, BCG vaccination, and NTM infection and is safe in healthy volunteers.

FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

PubMed

Seiler, Gabriela S; Campbell, Nigel; Nixon, Britton; Tsuruta, James K; Dayton, Paul A; Jennings, Samuel; Redding, W Rich; Lustgarten, Meghann

2016-05-01

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. © 2016 American College of Veterinary Radiology.

PRA (Probabilistic Risk Assessment) Applications Program for inspection at Oconee Unit 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gore, B.F.; Vo, T.V.; Harris, M.S.

1987-10-01

The extensive Oconee-3 PRA performed by EPRI has been analyzed to identify plant systems and components important to minimizing public risk, and to identify the primary failure modes of these components. This information has been tabulated, and correlated with inspection modules from the NRC Inspection and Enforcement Manual. The report presents a series of tables, organized by system and prioritized by public risk (in person-rem per year), which identify components associated with 98% of the inspectable risk due to plant operation. External events (earthquakes, tornadoes, fires and floods) are not addressed because inspections cannot directly minimize the risks from thesemore » events; however, flooding caused by the breach of internal systems is addressed. The systems addressed, in descending order of risk importance, are: Reactor Building Spray, R B Cooling, Condenser Circulating Water, Safety Relief Valves, Low Pressure Injection, Standby Shutdown Facility-High Pressure Injection, Low-Pressure Service Water, and Emergency Feedwater. This ranking is based on the Fussel-Vesely measure of risk importance, i.e., the fraction of the total risk which involves failures of the system of interest. 8 refs., 25 tabs.« less

The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study.

PubMed

Gaston, R Glenn; Larsen, Søren Erik; Pess, Gary M; Coleman, Stephen; Dean, Brian; Cohen, Brian M; Kaufman, Gregory J; Tursi, James P; Hurst, Lawrence C

2015-10-01

To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs). Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized. The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension. Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT): evaluating injectable methadone and injectable heroin treatment versus optimised oral methadone treatment in the UK

PubMed Central

Lintzeris, Nicholas; Strang, John; Metrebian, Nicola; Byford, Sarah; Hallam, Christopher; Lee, Sally; Zador, Deborah

2006-01-01

Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of illicit heroin in months 4 to 6). Secondary outcomes include measures of other drug use, injecting practices, health and psychosocial functioning, criminal activity, patient satisfaction and incremental cost effectiveness. The study aims to recruit 150 subjects, with 50 patients per group, and is to be conducted in supervised injecting clinics across England. PMID:17002810

Modeling and Fault Simulation of Propellant Filling System

NASA Astrophysics Data System (ADS)

Jiang, Yunchun; Liu, Weidong; Hou, Xiaobo

2012-05-01

Propellant filling system is one of the key ground plants in launching site of rocket that use liquid propellant. There is an urgent demand for ensuring and improving its reliability and safety, and there is no doubt that Failure Mode Effect Analysis (FMEA) is a good approach to meet it. Driven by the request to get more fault information for FMEA, and because of the high expense of propellant filling, in this paper, the working process of the propellant filling system in fault condition was studied by simulating based on AMESim. Firstly, based on analyzing its structure and function, the filling system was modular decomposed, and the mathematic models of every module were given, based on which the whole filling system was modeled in AMESim. Secondly, a general method of fault injecting into dynamic system was proposed, and as an example, two typical faults - leakage and blockage - were injected into the model of filling system, based on which one can get two fault models in AMESim. After that, fault simulation was processed and the dynamic characteristics of several key parameters were analyzed under fault conditions. The results show that the model can simulate effectively the two faults, and can be used to provide guidance for the filling system maintain and amelioration.

Intraseptal anesthesia: a review of a relevant injection technique.

PubMed

Woodmansey, Karl

2005-01-01

Although overshadowed by intraosseous anesthesia and the periodontal ligament injection, intraseptal anesthesia remains a useful local anesthesia technique for general dentists. Intraseptal anesthesia can be employed with safety and efficacy as an alternative to conventional local infiltration or regional nerve block injections. It also can serve as an adjunctive technique when conventional techniques fail to achieve adequate local anesthesia. This article reviews the intraseptal anesthesia technique, including its indications and limitations.

Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

PubMed

Mimoun, Gérard; Ebran, Jean-Marc; Grenet, Typhaine; Donati, Alain; Cohen, Salomon-Yves; Ponthieux, Anne

2017-08-01

To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats.

PubMed

Haidar, Ziyad S; Hamdy, Reggie C; Tabrizian, Maryam

2010-04-01

A hybrid, localized and release-controlled delivery system for bone growth factors consisting of a liposomal core incorporated into a shell of alternating layer-by-layer self-assembled natural polyelectrolytes has been formulated. Hydrophilic, monodisperse, spherical and stable cationic nanoparticles (< or =350 nm) with an extended shelf-life resulted. Cytocompatibility was previously assayed with MC3T3-E1.4 mouse preosteoblasts showing no adverse effects on cell viability. In this study, the in vivo biocompatibility of unloaded and loaded nanoparticles with osteogenic protein-1 or OP-1 was investigated. Young male Wistar rats were injected intramuscularly and monitored over a period of 10 weeks for signs of inflammation and/or adverse reactions. Blood samples (600 microL/collection) were withdrawn followed by hematological and biochemical analysis. Body weight changes over the treatment period were noted. Major organs were harvested, weighed and examined histologically for any pathological changes. Finally, the injection site was identified and examined immunohistochemically. Overall, all animals showed no obvious toxic health effects, immune responses and/or change in organ functions. This hybrid core-shell nanoparticulate delivery system localizes the effect of the released bioactive load within the site of injection in muscle with no significant tissue distress. Hence, a safe and promising carrier for therapeutic growth factors and possibly other biomolecules is presented. 2009 Elsevier Ltd. All rights reserved.

[On relationship of acupoint-injection with injury of peripheral nerves].

PubMed

Guo, Chang-Qing; Chen, You-Nan

2007-04-01

To provide basis for strengthening safety of acupoint-injection and increasing clinical therapeutic effect. Analyze and study on the relative articles from the databank of whole articles of Chinese periodicals of CNKI by information retrieval with computer, with acupoint-injection, nerve injury as key words. Most of clinical reports focus on acupoint-injection for treatment of nervous injury induced by trauma and birth injury. The studies indicate that the injuries of the peripheral nerves induced by acupoint-injection can be divided into 3 grades and the injury mechanisms can be divided into 3 classifications. The injuring causes include improper posture of the patients, improper angle and depth of injection and improper medicine selection. Acupoint-injection can be applied more widely as soon as the accomplishment of the standardization of operation.

A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.

PubMed

Greenberg, Richard N; Hay, Christine M; Stapleton, Jack T; Marbury, Thomas C; Wagner, Eva; Kreitmeir, Eva; Röesch, Siegfried; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P; Schmidt, Darja; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2016-01-01

Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18-55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. ClinicalTrials.gov NCT00857493.

Switching stable patients with schizophrenia from their oral antipsychotics to aripiprazole lauroxil: a post hoc safety analysis of the initial 12-week crossover period.

PubMed

Weiden, Peter J; Du, Yangchun; Liu, Chih-Chin; Stanford, Arielle D

2018-06-26

Switching antipsychotic medications is common in patients with schizophrenia who are experiencing persistent symptoms or tolerability issues associated with their current drug regimen. This analysis assessed the safety of switching from an oral antipsychotic to the long-acting injectable antipsychotic aripiprazole lauroxil (AL). This was a post hoc analysis of outpatients with schizophrenia who were prescribed an oral antipsychotic and who enrolled in an international, open-label, long-term (52-week) safety study of AL. The analysis focused on the first 3 injections of AL 882 mg over 12 weeks, divided into the immediate 4-week crossover period between the first and second AL injections (initiation phase) and the subsequent 8 weeks (stabilization phase). Patients were grouped by preswitch oral antipsychotic medication, and safety and clinical symptoms were assessed. In total, 190 patients had switched from one of the following oral antipsychotic medications: aripiprazole, conventional antipsychotics, risperidone/paliperidone, olanzapine, or quetiapine. The 12-week completion rate was high (92.1%) and similar across the different preswitch oral antipsychotic groups. Overall, adverse event (AE) rates experienced over 12 weeks were modest; no AEs were considered serious. The most common AEs in the initiation phase were injection site pain (5.8%), insomnia (5.8%), and akathisia (3.2%). No apparent relationship was observed between preswitch medication and early-onset AEs. Mean Positive and Negative Syndrome Scale total scores remained stable during this period across preswitch antipsychotic groups. Switching from an oral antipsychotic to AL was feasible in an outpatient setting for patients with schizophrenia, and the 12-week retention rate was favorable.

Safety Profile of Collagenase Clostridium Histolyticum Stratified by Degree of Penile Curvature in Patients With Peyronie Disease.

PubMed

Hellstrom, Wayne J G; Tan, Ronny B W; Liu, Genzhou

2017-08-01

To examine the safety of collagenase clostridium histolyticum (CCH) in adult men with penile curvature deformity <30°. CCH is indicated for treatment of Peyronie disease in adult men with palpable plaque and a penile curvature deformity ≥30° at start of therapy; however, during treatment, patients may receive CCH injections when penile curvature deformity is <30°. Patients who received ≥2 CCH treatment cycles in 2 phase 3 studies (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II) were included. All patients had penile curvature ≥30° at the beginning of treatment and could receive up to 4 treatment cycles. The rate and number of treatment-related adverse events (TRAEs) with CCH treatment were compared between patients with penile curvature deformity ≥30° and penile curvature <30°. The number of CCH treatment cycles included in the current analysis totaled 1204 and 289 cycles in patients with penile curvature deformity ≥30° and <30°, respectively. The incidence of most TRAEs was similar between groups. Rates of penile swelling (21.1% vs 14.5%, P = .007), penile hemorrhage (12.8% vs 8.9%; P = .046), and skin hyperpigmentation (1.0% vs 0.1%; P = .025) were significantly higher in the <30° group. The occurrence of serious TRAEs was similar between groups. No clinically meaningful differences were observed with TRAE rates when CCH injections were administered at penile curvature deformity ≥30° vs CCH injections at penile curvature deformity <30°. These findings highlight the safety of continued CCH injections for patients who have achieved penile curvature deformity <30° after an initial treatment cycle of CCH. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Efficacy and safety of point-of-care ultrasound-guided intra-articular corticosteroid joint injections in patients with haemophilic arthropathy.

PubMed

Martin, E J; Cooke, E J; Ceponis, A; Barnes, R F W; Moran, C M; Holle, S; Hughes, T H; Moore, R E; von Drygalski, A

2017-01-01

Intra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy. Ultrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications. Forty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity. Point-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy. © 2016 John Wiley & Sons Ltd.

IRay therapy as an adjuvant therapy in newly diagnosed patients with neovascular age-related macular degeneration.

PubMed

Brand, Christopher; Arnoldussen, Mark

2018-04-17

To determine the safety and efficacy at 12 months of follow-up after stereotactic radiotherapy in combination therapy with intravitreal ranibizumab injections in treatment naïve patients with neovascular age-related macular degeneration. Retrospective data analysis in patients who received stereotactic radiotherapy (IRay Therapy) during the induction phase of intravitreal ranibizumab injections and a monotherapy control group. The baseline VA in the IRay and control group was 59.87 and 59.12 letters respectively. The real world visual acuity outcomes for the IRay group showed a mean gain of +3.0 letters at 12 months. The historical control group had a mean change of - 0.3 letters. The average number of injections for the IRay group and control group over 12 months was 4.45 and 5.64, respectively with three loading injections. Excluding the loading phase, the difference over 12 months was a 45.2% reduction in injections (P < 0.001). The number of subjects in the IRay group that didn't require further injections following the loading phase was 45.5 vs. 24.0% control group (P = 0.005). The difference in mean change in central macular thickness from baseline is significant at 6 (P = 0.010) and 12 months (P < 0.01). There were no safety concerns with the IRay therapy group. Stereotactic radiotherapy in the induction phase of intravitreal injections of ranibizumab for treatment naïve patients with neovascular age-related macular degeneration, resulted in improved visual outcome, statistically fewer injections and statistically drier macular at 12 months, compared to historical controls treated with monotherapy intravitreal ranibizumab injections.

Application of propensity scores to estimate the association between government subsidy and injection use in primary health care institutions in China.

PubMed

Tang, Yuqing; Zhang, Xiaopeng; Yang, Chunyan; Yang, Lianping; Wang, Hongtao; Zhang, Xinping

2013-05-21

The problem posed by therapeutic injection is a clinical practice issue that influences health care quality and patient safety. Although sufficient government subsidy was one of the 12 key interventions to promote rational drug use initiated by WHO (World Health Organization), limited information is available about the association between government subsidy and injection use in primary health care institutions. In 2009, National Essential Medicines System (NEMS) was implemented in China. The subsidy policy plays an important role in maintaining primary health care institutions. This study explores the impact of government subsidies on the injection use in primary health care institutions in China. 126 primary health institutions were included in this study. Institutions were divided into two groups (intervention and control groups) according to the median GS (General subsidy per personnel). Propensity score matching (PSM) was used to minimize the observed covariate differences in the characteristics of the primary institutions between the two groups. Kappa score was calculated to determine the consistency between the groups. Paired chi-square test and Relative Risk (RR) were calculated to compare the differences in injection use between the groups. Among all the investigated prescriptions, the overall percent of people who received an injection prescribed was 36.96% (n = 12600). PSM showed no significant covariate difference among the 34 groups obtained through this analysis. Kappa score (k = -0.082, p = 0.558) indicated an inconsistency between groups and paired chi-square test revealed a significant difference (p < 0.05) in injection use between the two groups. Relative Risk = 0.679 (95%CI [0.485, 0.950]) indicate that high General subsidy per personnel is a protective factor for primary health care institutions to prescribe injections properly. The intervention group obtained a higher possibility of using injection properly. The overall effect of government subsidy on the use of injection was positively significant. However, the mechanism by which government subsidy influence injection administration remains unclear, and thus requires further study.

Postmarketing Safety Surveillance and Reevaluation of Danhong Injection: Clinical Study of 30888 Cases

PubMed Central

Li, Xue-Lin; Tang, Jin-Fa; Li, Wei-Xia; Li, Chun-Xiao; Zhao, Tao; Zhao, Bu-Chang; Wang, Yong; Zhang, Hui; Chen, Xiao-Fei; Xu, Tao; Zhu, Ming-Jun

2015-01-01

Traditional Chinese medicine injections (TCMIs) have played an irreplaceable role for treating some clinical emergency, severe illness, and infectious diseases in China. In recent years, the incidence rates of adverse drug reactions (ADRs) of TCMIs have increased year by year. Danhong injection (DHI) is one representative TCMI comprised of Danshen and Honghua for treating cardiovascular and cerebrovascular diseases in clinic. In present study, the postmarketing safety surveillance and reevaluation of DHI were reported. Total 30888 patients in 37 hospitals from 6 provinces participated in the study. The results showed that the ADR incidence rate of DHI was 3.50‰. Seventeen kinds of new adverse reactions of DHI were found. The main type of ADRs of DHI was type A (including sweating, dizziness, headache, flushing, vasodilation, eye hemorrhage, faintness, chest pain, palpitations, breathlessness, anxious, nausea, flatulence, vomiting, hypotension, hypertension, local numbness, dyspnea, joint disease, and tinnitus) accounting for 57.75%. The severities of most ADRs of DHI were mild and moderate reactions accounting for 25.93% and 66.67%, respectively. The main disposition of ADRs of DHI was drug withdrawal and without any treatments. The results can provide basis for amendment and improvement of the instructions of DHI, as well as demonstration and reference for the postmarketing safety surveillance and reevaluation of other TCMIs. And the rationality, scientificity, and safety of clinical applications of TCMIs could be improved. PMID:26508981

A retrospective, pooled data analysis of the safety of pegaptanib sodium in the treatment of age-related macular degeneration in subjects with or without diabetes mellitus.

PubMed

Dombi, Theresa; Kwok, Kenneth K; Sultan, Marla B

2012-08-08

To evaluate the safety of pegaptanib sodium 0.3 mg intravitreal injection in the treatment of neovascular age-related macular degeneration in subjects with or without diabetes mellitus. A pooled, retrospective, analysis was conducted of data from 9 sponsor-administered, randomized, open-label trials. Subjects who received pegaptanib by randomization or change in dose assignment, crossover design, or protocol amendment, were included. Reports of endophthalmitis, increased intraocular pressure, retinal injury, intraocular hemorrhage, traumatic cataract, hypersensitivity reactions, stroke, myocardial infarction, and other arterial thromboembolic events defined by the Antiplatelet Trialists' Collaboration were identified by Medical Dictionary for Regulatory Activities preferred terms. Adverse events were summarized from the first injection to 42 days after the last injection. The incidence of adverse events was stratified by the presence/absence of diabetes. Of 1,586 subjects enrolled, 165 (10.4%) had a history of diabetes mellitus and 1,421 (89.6%) did not. The 2 populations were similar at baseline. Based on the comparison of prespecified ocular, hypersensitivity, and Antiplatelet Trialists' Collaboration event terms, the safety review did not identify any notable differences between the 2 populations. This retrospective analysis found no increased safety risk resulting from treatment with pegaptanib 0.3 mg in individuals with neovascular age-related macular degeneration and concomitant diabetes mellitus.

Occupational Safety in the Age of the Opioid Crisis: Needle Stick Injury among Baltimore Police.

PubMed

Cepeda, Javier A; Beletsky, Leo; Sawyer, Anne; Serio-Chapman, Chris; Smelyanskaya, Marina; Han, Jennifer; Robinowitz, Natanya; Sherman, Susan G

2017-02-01

At a time of resurgence in injection drug use and injection-attributable infections, needle stick injury (NSI) risk and its correlates among police remain understudied. In the context of occupational safety training, a convenience sample of 771 Baltimore city police officers responded to a self-administered survey. Domains included NSI experience, protective behaviors, and attitudes towards syringe exchange programs. Sixty officers (8%) reported lifetime NSI. Officers identifying as Latino or other race were almost three times more likely (aOR 2.58, 95% CI 1.12-5.96) to have experienced NSI compared to whites, after adjusting for potential confounders. Findings highlight disparate burdens of NSIs among officers of color, elevating risk of hepatitis, HIV, and trauma. Training, equipment, and other measures to improve occupational safety are critical to attracting and safeguarding police, especially minority officers.

Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal/stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacIsaac, Zoe Marie, E-mail: zmm4a@virgina.edu; Shang, Hulan, E-mail: shanghulan@gmail.com; Agrawal, Hitesh, E-mail: hiteshdos@hotmail.com

2012-02-15

After more than a decade of extensive experimentation, the promise of stem cells to revolutionize the field of medicine has negotiated their entry into clinical trial. Adipose tissue specifically holds potential as an attainable and abundant source of stem cells. Currently undergoing investigation are adipose stem cell (ASC) therapies for diabetes and critical limb ischemia, among others. In the enthusiastic pursuit of regenerative therapies, however, questions remain regarding ASC persistence and migration, and, importantly, their safety and potential for neoplasia. To date, assays of in vivo ASC activity have been limited by early end points. We hypothesized that with time,more » ASCs injected subcutaneously undergo removal by normal tissue turnover and homeostasis, and by the host's immune system. In this study, a high dose of culture expanded ASCs was formulated and implanted as multicellular aggregates into immunocompromised mice, which were maintained for over one year. Animals were monitored for toxicity, and surviving cells quantified at study endpoint. No difference in growth/weight or lifespan was found between cell-treated and vehicle treated animals, and no malignancies were detected in treated animals. Moreover, real-time PCR for a human specific sequence, ERV-3, detected no persistent ASCs. With the advent of clinical application, clarification of currently enigmatic stem cell properties has become imperative. Our study represents the longest duration determination of stem cell activity in vivo, and contributes strong evidence in support of the safety of adipose derived stem cell applications. -- Highlights: Black-Right-Pointing-Pointer Adipose stem cells promise novel clinical therapies. Black-Right-Pointing-Pointer Before clinical translation, safety profiles must be further elucidated. Black-Right-Pointing-Pointer Subcutaneously injected non-autologous adipose stem cells do not form tumors. Black-Right-Pointing-Pointer Subcutaneously injected non-autologous adipose stem cells undergo complete removal by one year.« less

Therapeutic Outcome of Intralesional Immunotherapy in Cutaneous Warts Using the Mumps, Measles, and Rubella Vaccine

PubMed Central

Awal, Guneet

2018-01-01

Background: Various treatment modalities have been described in the literature for treating warts, but none thus far have demonstrated optimal results. Recently, the mumps, measles, and rubella (MMR) antigen has gained popularity because of its proven efficacy in the treatment of warts. Aim: The goal was to evaluate the efficacy and safety of intralesional MMR antigen in the treatment of cutaneous warts. Methods: Patients were divided into an MMR (study) group and a normal saline (control) group. Injections were administered into the single largest wart on each patient every two weeks. Follow-up was done at six weeks and 16 weeks after the last injection for any side effects and/or recurrence. Results: Out of 150 patients, 72 received the MMR injection and 50 received normal saline injections. Twenty-eight patients did not complete the study. A statistically significant (p<0.00001) difference in results was found between the two groups: 68 percent of patients in the MMR group showed complete response compared to 10 percent in the control group. Pain during injection was the most common side effect and was seen in both groups. Conclusion: MMR injection has shown significant results with almost negligible adverse effects. The MMR antigen vaccine has therapeutic potential as a treatment for warts with its demonstrated efficacy, safety profile, and cost-effectiveness. PMID:29785233

Injection practices in Nepal: health policymakers’ perceptions

PubMed Central

2014-01-01

Background The unnecessary and unsafe use of injections is common in developing countries like Nepal. Policymakers have an important role in promoting rational and safe injection use. Hence, the present study was carried out to explore the perception of health policymakers regarding safe injection practice in Nepal. Methods An exploratory qualitative study design was used in this study. Key policymakers from both the central and regional level were selected using purposive sampling. A semi-structured questionnaire advocated by the World Health Organization (WHO) was used after modifying the context. Interviews were conducted to clarify doubts and obtain additional information. The data was analyzed manually using deductive content analysis technique. Results In total, eleven policymakers participated. All unanimously agreed that injection safety is a problem and seven participants reported that injections are overused. They shared the opinion that injections are administered by various providers, including formal and informal health providers, and also quacks. Almost half the respondents reported that the National Drug Policy discourages injection overuse, while others reported that the policy contains no provisions regarding injection overuse. Most policymakers stated that only single-use disposable injection equipment is used to provide injection, while others thought that sterilizable glass syringe is also used. More than half of the participants believed that the quality of injection equipment available in the Nepalese market is not regulated by any government institution. Almost two-third of the policymakers stated that syringes and needles are not reused, while the rest thought syringes might be reused without sterilization in some parts of the country. Almost half of the respondents stated that illegal commercialization of used syringes exists in Nepal. Almost all respondents thought that health care institutions have a waste management plan, while more than half of them opined that such plans are limited to tertiary care hospitals located in the capital. Conclusions The result of this study revealed a divergence of views among policymakers, even among those in the same ministry. Though there has been some effort from the government to increase the safety of injection practices, greater efforts are required, especially with regard to standardization of policies and procedures related to injection practice. PMID:24957575

Injection practices in Nepal: health policymakers' perceptions.

PubMed

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, Pathiyil Ravi; Maskey, Manisha; Vikash, Kumar K C

2014-06-24

The unnecessary and unsafe use of injections is common in developing countries like Nepal. Policymakers have an important role in promoting rational and safe injection use. Hence, the present study was carried out to explore the perception of health policymakers regarding safe injection practice in Nepal. An exploratory qualitative study design was used in this study. Key policymakers from both the central and regional level were selected using purposive sampling. A semi-structured questionnaire advocated by the World Health Organization (WHO) was used after modifying the context. Interviews were conducted to clarify doubts and obtain additional information. The data was analyzed manually using deductive content analysis technique. In total, eleven policymakers participated. All unanimously agreed that injection safety is a problem and seven participants reported that injections are overused. They shared the opinion that injections are administered by various providers, including formal and informal health providers, and also quacks. Almost half the respondents reported that the National Drug Policy discourages injection overuse, while others reported that the policy contains no provisions regarding injection overuse. Most policymakers stated that only single-use disposable injection equipment is used to provide injection, while others thought that sterilizable glass syringe is also used. More than half of the participants believed that the quality of injection equipment available in the Nepalese market is not regulated by any government institution. Almost two-third of the policymakers stated that syringes and needles are not reused, while the rest thought syringes might be reused without sterilization in some parts of the country. Almost half of the respondents stated that illegal commercialization of used syringes exists in Nepal. Almost all respondents thought that health care institutions have a waste management plan, while more than half of them opined that such plans are limited to tertiary care hospitals located in the capital. The result of this study revealed a divergence of views among policymakers, even among those in the same ministry. Though there has been some effort from the government to increase the safety of injection practices, greater efforts are required, especially with regard to standardization of policies and procedures related to injection practice.

Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis.

PubMed

Sufit, Robert L; Ajroud-Driss, Senda; Casey, Patricia; Kessler, John A

2017-05-01

To assess safety and define efficacy measures of hepatocyte growth factor (HGF) DNA plasmid, VM202, administered by intramuscular injections in patients with amyotrophic lateral sclerosis (ALS). Eighteen participants were treated with VM202 administered in divided doses by injections alternating between the upper and lower limbs on d 0, 7, 14, and 21. Subjects were followed for nine months to evaluate possible adverse events. Functional outcome was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) as well as by serially measuring muscle strength, muscle circumference, and forced vital capacity. Seventeen of 18 participants completed the study. All participants tolerated 64 mg of VM202 well with no serious adverse events (SAE) related to the drug. Twelve participants reported 26 mild or moderate injection site reactions. Three participants experienced five SAEs unrelated to VM202. One subject died from respiratory insufficiency secondary to ALS progression. Multiple intramuscular injection of VM202 into the limbs appears safe in ALS subjects. Future trials with retreatment after three months will determine whether VM202 treatment alters the long-term course of ALS.

The Accident at TEPCO's Fukushima-Daiichi Nuclear Power Plant: Technical Description of What Happened and Lessons Learned for the Future

NASA Astrophysics Data System (ADS)

Omoto, Akira

2012-02-01

Tsunami that followed M9.0 earthquake on March 11^th left the Fukushima-Daiichi Nuclear Power Plants without power and heat sink. While water makeup continued by AC-independent systems to keep the fuel core covered by coolant, operating team tried to depressurize and enable low pressure injection to the reactor to avoid overheating but was not successful enough primarily due to limited available resources. This resulted in core melt, hydrogen explosion and release of radioactivity to the environment. Key lessons learned are; 1) safety regulation and safety culture, 2) workable/executable severe accident management procedure, 3) crisis management and 4) design. Implications on security include revealed vulnerability and the nexus of safety and security. Given the scale of damage to the environmental, attention must be paid to defense against it and to societal safety goal of nuclear power by considering offsite remedial costs, compensation to damage, energy replacement cost etc. A sort of root cause analysis first by asking ``Why nuclear community failed to prevent this accident?'' was initiated by the University of Tokyo.

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Yanxin; Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122; Guo, Huanhuan

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beaglemore » cardiovascular and respiratory systems at 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 10{sup 10} VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 10{sup 10} VP/kg) and beagles (2.5 × 10{sup 9} VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 10{sup 10} VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 10{sup 8} VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad-hTERT-E1a-Apoptin.« less

Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch.

PubMed

Hirobe, Sachiko; Azukizawa, Hiroaki; Hanafusa, Takaaki; Matsuo, Kazuhiko; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Okada, Naoki; Nakagawa, Shinsaku

2015-07-01

Transcutaneous immunization (TCI) is an attractive vaccination method compared with conventional injectable vaccines because it is easier to administer without pain. We developed a dissolving microneedle patch (MicroHyala, MH) made of hyaluronic acid and showed that transcutaneous vaccination using MH induced a strong immune response against various antigens in mice. In the present study, we investigated the clinical safety and efficacy of a novel transcutaneous influenza vaccine using MH (flu-MH), which contains trivalent influenza hemagglutinins (15 μg each). Subjects of the TCI group were treated transcutaneously with flu-MH, and were compared with subjects who received subcutaneous injections of a solution containing 15 μg of each influenza antigen (SCI group). No severe local or systemic adverse events were detected in either group and immune responses against A/H1N1 and A/H3N2 strains were induced equally in the TCI and SCI groups. Moreover, the efficacy of the vaccine against the B strain in the TCI group was stronger than that in the SCI group. Influenza vaccination using MH is promising for practical use as an easy and effective method to replace conventional injections systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars.

PubMed

Grampp, Gustavo; Bonafede, Machaon; Felix, Thomas; Li, Edward; Malecki, Michael; Sprafka, J Michael

2015-03-01

This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs). Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers. Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share. Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

Application of reliability-centered-maintenance to BWR ECCS motor operator valve performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feltus, M.A.; Choi, Y.A.

1993-01-01

This paper describes the application of reliability-centered maintenance (RCM) methods to plant probabilistic risk assessment (PRA) and safety analyses for four boiling water reactor emergency core cooling systems (ECCSs): (1) high-pressure coolant injection (HPCI); (2) reactor core isolation cooling (RCIC); (3) residual heat removal (RHR); and (4) core spray systems. Reliability-centered maintenance is a system function-based technique for improving a preventive maintenance program that is applied on a component basis. Those components that truly affect plant function are identified, and maintenance tasks are focused on preventing their failures. The RCM evaluation establishes the relevant criteria that preserve system function somore » that an RCM-focused approach can be flexible and dynamic.« less

A Flight Control System Architecture for the NASA AirSTAR Flight Test Infrastructure

NASA Technical Reports Server (NTRS)

Murch, Austin M.

2008-01-01

A flight control system architecture for the NASA AirSTAR infrastructure has been designed to address the challenges associated with safe and efficient flight testing of research control laws in adverse flight conditions. The AirSTAR flight control system provides a flexible framework that enables NASA Aviation Safety Program research objectives, and includes the ability to rapidly integrate and test research control laws, emulate component or sensor failures, inject automated control surface perturbations, and provide a baseline control law for comparison to research control laws and to increase operational efficiency. The current baseline control law uses an angle of attack command augmentation system for the pitch axis and simple stability augmentation for the roll and yaw axes.

Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

PubMed

Tellegen, Anna R; Willems, Nicole; Beukers, Martijn; Grinwis, Guy C M; Plomp, Saskia G M; Bos, Clemens; van Dijk, Maarten; de Leeuw, Mike; Creemers, Laura B; Tryfonidou, Marianna A; Meij, Björn P

2018-03-01

Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

PubMed Central

Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

2016-01-01

Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371

Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review.

PubMed

Altman, Roy; Hackel, Josh; Niazi, Faizan; Shaw, Peter; Nicholls, Mathew

2018-01-31

Hyaluronic acid (HA) is a commonly prescribed intra-articular (IA) therapy for knee osteoarthritis (OA). While a single series of IA-HA has been well studied, the efficacy and safety of repeated courses of IA-HA injection therapy in knee OA patients have not been evaluated as frequently. A literature search was conducted using MEDLINE, EMBASE and PubMed databases. The primary outcome measure was knee pain reduction after each treatment course and/or last reported follow-up visit. Secondary outcomes were treatment-related adverse events (AEs) and serious adverse events (SAEs). A total of 17 articles (7 RCTs and 10 cohort studies) met the pre-defined inclusion criteria. Of the RCTs, six were double-blind with two trials including open label extension studies, and one was single-blind. Studies ranged from investigating a single reinjection cycle to four repeat injection cycles. Eleven studies evaluated one reinjection, five studies evaluated ≥2 repeated courses of IA-HA, and one study allowed either one or two repeated courses. All studies reported pain reduction from baseline in the IA-HA treatment group throughout the initial treatment cycle, and either sustained or further reduced pain throughout the repeated courses of treatment. The study with the longest follow-up repeated IA-HA injection every 6 months for 25 months. Pain decreased after the first course and continued to decrease until the end of the study, with an approximate 55% reduction in pain compared to baseline. Common AEs were joint swelling and arthralgia; there were no reported SAEs. All repeated courses were well tolerated, and the number of documented AEs and SAEs was similar to the primary injection regimens. Repeated courses of IA-HA injections are an effective and safe treatment for knee OA. Repeat courses were demonstrated to maintain or further improve pain reduction while introducing no increased safety risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Alopecia with foreign body granulomas induced by Radiesse injection: A case report.

PubMed

Liu, Ren-Feng; Kuo, Tseng-Tong; Chao, Yen-Yu; Huang, Yu-Huei

2018-02-26

Radiesse is a soft tissue filler which has been widely used for cosmetic enhancement. The safety of Radiesse has been thoroughly investigated via numerous studies. A late-onset complication of Radiesse injection consists of foreign body granulomas, with only three case reports in over 10 years of clinical use. Herein, we describe the case of a patient who experienced alopecia with foreign body granulomas at the injection region one month after receiving a Radiesse injection. To our knowledge, this is the first report in the English literature of alopecia as an adverse event associated with Radiesse injection. The present case reminded physicians to evaluate more cautiously the necessity of injecting filler into hair-bearing area for lifting purpose. This procedure may cause foreign body granulomatous reaction, which may result in hair loss at the injection region.

A next-generation, serum-free, highly purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab® when administered according to a post-exposure regimen in healthy children and adults in China.

PubMed

Li, Rongcheng; Huang, Lirong; Li, Jia; Mo, Zhaojun; He, Bin; Wang, Yunpeng; Wu, Xiaohong; Minutello, Maria; Guinet-Morlot, Françoise; Pichon, Sylvie

2013-12-05

As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the study. An abstract of the study results was previously presented at the Rabies in the Americas (RITA) conference in October 2012 in São Paulo, Brazil. Sanofi Pasteur. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity

PubMed Central

Cho, Young Sam; Kim, Khae Hawn

2016-01-01

Evidence for the efficacy and safety of intravesical onabotulinum toxin A (onabotA) injections has led to them being licensed in many countries, including Korea, for the treatment of patients with urinary incontinence due to neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or multiple sclerosis who are refractory or intolerant to anticholinergic medications. OnabotA injections have an inhibitory effect on acetylcholine release for up to 10 months, with a recommended dose of 200 U. OnabotA treatment has a beneficial effect not only on urinary symptoms, but also on quality of life. Several clinical studies have shown onabotA to have better effects than placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters, and improving health-related quality of life. Urinary tract infections and postvoid residual volume are the most prevalent side effects. In patients with residual volume, clean intermittent catheterization may be necessary. In patients with spinal cord injury or multiple sclerosis, it is recommended to evaluate physical and cognitive function before intravesical onabotA injection to ensure that the patient and caregiver are able to perform catheterization if necessary. Further controlled trials should assess the optimal dose, injection technique, long-term safety of repeated injections, and optimal timing of onabotA treatment in the treatment of NDO. PMID:28119887

[Safety and effectiveness of large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors].

PubMed

Li, Dao-rui; Lin, Hong-sheng

2011-04-01

To evaluate the effectiveness and safety of large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors. A non-randomized case control trial was conducted. Ninety six patients with pathologically confirmed advanced non-small-cell lung cancer, gastric cancer and colorectal cancer were divided into traditional Chinese medicine group and chemotherapy group, 48 cases each. Patients of the traditional Chinese medicine group received treatment with large dose of compound Sophora flavescens Ait injection (20 ml/d), and 21 days as a cycle. Forty-seven patients of the traditional Chinese medicine group and 46 patients of the chemotherapy group completed their treatment, respectively. The clinical benefit rate (CBR) in the traditional Chinese medicine group was 83.0%, significantly higher than that in the chemotherapy group (69.6%) (P < 0.01). The Karnofsky performance status and weight improvement in the traditional Chinese medicine group was superior to that in the chemotherapy group (P < 0.05). Except the skin irritation in one patient in the traditional Chinese medicine group, there were no other clinical adverse effects related with the large dose compound Sophora flavescens Ait injection. Large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors is safe and effective. The recommended dose is 20 ml/d.

Injectable nanocomposite cryogels for versatile protein drug delivery.

PubMed

Koshy, Sandeep T; Zhang, David K Y; Grolman, Joshua M; Stafford, Alexander G; Mooney, David J

2018-01-01

Sustained, localized protein delivery can enhance the safety and activity of protein drugs in diverse disease settings. While hydrogel systems are widely studied as vehicles for protein delivery, they often suffer from rapid release of encapsulated cargo, leading to a narrow duration of therapy, and protein cargo can be denatured by incompatibility with the hydrogel crosslinking chemistry. In this work, we describe injectable nanocomposite hydrogels that are capable of sustained, bioactive, release of a variety of encapsulated proteins. Injectable and porous cryogels were formed by bio-orthogonal crosslinking of alginate using tetrazine-norbornene coupling. To provide sustained release from these hydrogels, protein cargo was pre-adsorbed to charged Laponite nanoparticles that were incorporated within the walls of the cryogels. The presence of Laponite particles substantially hindered the release of a number of proteins that otherwise showed burst release from these hydrogels. By modifying the Laponite content within the hydrogels, the kinetics of protein release could be precisely tuned. This versatile strategy to control protein release simplifies the design of hydrogel drug delivery systems. Here we present an injectable nanocomposite hydrogel for simple and versatile controlled release of therapeutic proteins. Protein release from hydrogels often requires first entrapping the protein in particles and embedding these particles within the hydrogel to allow controlled protein release. This pre-encapsulation process can be cumbersome, can damage the protein's activity, and must be optimized for each protein of interest. The strategy presented in this work simply premixes the protein with charged nanoparticles that bind strongly with the protein. These protein-laden particles are then placed within a hydrogel and slowly release the protein into the surrounding environment. Using this method, tunable release from an injectable hydrogel can be achieved for a variety of proteins. This strategy greatly simplifies the design of hydrogel systems for therapeutic protein release applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contingency Power Study for Short Haul Civil Tiltrotor

NASA Technical Reports Server (NTRS)

Eisenberg, Joseph D. (Technical Monitor); Wait, John

2003-01-01

AlliedSignal Engines (AE) defined a number of concepts that significantly increased the horsepower of a turboshaft engine to accommodate the loss of an engine and enable the safe landing of a twin-engined, 40-passenger, short haul civil tiltrotor. From these concepts, "Water/Methanol Injection," a "Better Power Turbine Than Required," and a "Secondary Combustor For Interturbine Reheat" were chosen, based on system safety and economics, for more detailed examination. Engine performance, mission, and cost analysis of these systems indicated contingency power levels of 26 to 70 percent greater than normal rated takeoff could be attained for short durations, thus enabling direct operating cost savings between 2 and 6 percent.

21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... guinea pigs, the test shall be satisfied if the product provides satisfactory results using either the subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea pig. The requirements for general safety for inactivated influenza vaccine shall not be considered to...

Double-Blind, Randomized Study of Safety and Efficacy of OnabotulinumtoxinA (OnaBoNT-A) versus Oral Oxybutynin in SCI Patients with NDO (11-09-10-04)

DTIC Science & Technology

2014-10-01

procedures in the clinic. The doctor wll decide if you will be given a local anesthesia to lessen the pain before beginning the injection procedure...injection and, while usually temporary, they may last several months. Pain , tenderness, or bruising around the injection site may also occur. Local weakness...indigestion; nausea; runny nose; stomach pain or upset; trouble sleeping; weakness Severe Side Effects: Severe allergic reactions (rash; hives

The safety of seasonal influenza vaccines in Australian children in 2013.

PubMed

Wood, Nicholas J; Blyth, Chris C; Willis, Gabriela A; Richmond, Peter; Gold, Michael S; Buttery, Jim P; Crawford, Nigel; Crampton, Michael; Yin, J Kevin; Chow, Maria Yui Kwan; Macartney, Kristine

2014-11-17

To examine influenza vaccine safety in Australian children aged under 10 years in 2013. Active prospective surveillance study conducted with parents or carers of children who received influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or from selected primary health care providers between 18 March and 19 July 2013. Parental-reported frequency of systemic reactions (fever, headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue), injection site reactions (erythema, swelling and/or pain at the injection site), use of antipyretics or analgesics, and medical attendance or advice within 72 hours after vaccination. Of 981 children enrolled in the surveillance, 893 children aged 6 months to < 10 years were eligible for inclusion. These children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95% CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2, respectively. One febrile convulsion occurred in a child with a known seizure disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and 6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95% CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2. These results are consistent with clinical trials and other observational studies of influenza vaccines currently registered for use in young children in Australia and can reassure parents and health care providers that influenza vaccination is safe and well tolerated.

Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency.

PubMed

Cohen-Barak, Orit; Sakov, Anat; Rasamoelisolo, Michele; Bassan, Merav; Brown, Kurt; Mendzelevski, Boaz; Spiegelstein, Ofer

2015-11-01

TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant protein of human GH (hGH) and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 is expected to have an extended duration of action compared to daily GH treatment and may enable a reduction in the frequency of injections and improve compliance and quality of life for adults and children requiring GHD therapy. To assess the safety, local tolerability, pharmacokinetics and pharmacodynamics of TV-1106 following single s.c. injections in healthy male volunteers. Subjects (n=56) were assigned to one of seven ascending dose groups (3-100 mg) and received either a single dose of TV-1106 (n=6) or placebo (n=2) by s.c. injection. Eighteen subjects reported 43 adverse effects (AEs), which were mild to moderate; no serious AEs (SAEs) occurred. In 50, 70 and 100 mg groups there were mild to moderate increases in heart rate and systolic blood pressure that significantly correlated with higher levels of IGF1. TV-1106 showed pharmacokinetic characteristics of a long-acting hGH as demonstrated by a terminal elimination half-life of 23-35 h, delayed time of peak concentration, and systemic levels seen up to 7 days after dosing. IGF1 levels increased in a dose-dependent manner, before reaching a plateau, with levels above baseline extending beyond 7 days post dose. Single administration of TV-1106 up to 100 mg was safe in healthy volunteers. Pharmacokinetics and pharmacodynamics support once-weekly administration in patients with GHD. © 2015 The authors.

Graphics enhanced computer emulation for improved timing-race and fault tolerance control system analysis. [of Centaur liquid-fuel booster

NASA Technical Reports Server (NTRS)

Szatkowski, G. P.

1983-01-01

A computer simulation system has been developed for the Space Shuttle's advanced Centaur liquid fuel booster rocket, in order to conduct systems safety verification and flight operations training. This simulation utility is designed to analyze functional system behavior by integrating control avionics with mechanical and fluid elements, and is able to emulate any system operation, from simple relay logic to complex VLSI components, with wire-by-wire detail. A novel graphics data entry system offers a pseudo-wire wrap data base that can be easily updated. Visual subsystem operations can be selected and displayed in color on a six-monitor graphics processor. System timing and fault verification analyses are conducted by injecting component fault modes and min/max timing delays, and then observing system operation through a red line monitor.

Agreement between a physiotherapist and an orthopaedic surgeon regarding management and prescription of corticosteroid injection for patients with shoulder pain.

PubMed

Marks, Darryn; Comans, Tracy; Thomas, Michael; Ng, Shu Kay; O'Leary, Shaun; Conaghan, Philip G; Scuffham, Paul A; Bisset, Leanne

2016-12-01

Physiotherapists increasingly manage shoulder referrals in place of orthopaedic doctors. Better understanding the agreement between these professionals will help inform the safety, quality and potential costs of these care models. To establish the level of agreement between a physiotherapist and an orthopaedic surgeon regarding diagnosis, management and corticosteroid injection, in a representative sample of orthopaedic shoulder referrals. Blinded inter-rater agreement study. 274 public orthopaedic shoulder patients were independently assessed by a physiotherapist and an orthopaedic surgeon. Management, subacromial corticosteroid injection, diagnosis and investigation decisions were compared using inter-rater reliability statistics. Agreement between the physiotherapist and the orthopaedic surgeon was near perfect for surgical versus nonsurgical management (Gwets agreement coefficient AC1 = 0.93, 95%CI: 0.90-0.93), safety of injection (AC1 = 0.85, CI: 0.79-0.91) and investigations requested (AC1 = 0.87, CI: 0.83-0.91); substantial for the presence of subacromial pain (AC1 = 0.74, CI: 0.66-0.81) and diagnosis (AC1 = 0.72, CI: 0.66-0.78); and moderate regarding delivery of subacromial corticosteroid injection as an immediate treatment (AC1 = 0.48, CI 0.33-0.53), with the physiotherapist less inclined to select corticosteroid injection as the first intervention. In this study a physiotherapist with prescribing and injection training made decisions analogous to those of an orthopaedic surgeon at initial consultation for orthopaedic shoulder pain, including the safe identification of patients for subacromial injection, without prior screening of referrals by orthopaedic doctors. Australia and New Zealand Clinical Trials Registry, number 12612000532808. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safety and Efficacy of Permacol Injection in the Treatment of Fecal Incontinence.

PubMed

Al-Abed, Yahya A; Ayers, Jennifer; Ayantunde, Abraham; Praveen, Bandipalyam V

2016-04-01

Permacol has been gaining popularity in recent times for the treatment of fecal incontinence (FI). This study aims to evaluate the safety and efficacy of anal submucosal Permacol injection in the treatment of FI. All consecutive patients who underwent Permacol injection for FI over a 3-year period were included. Patients' data relating to obstetric history, anorectal/pelvic operations, type of FI, preoperative anorectal physiology results and follow-up details for outcome measures were collected. Preoperative and postoperative Cleveland Clinic Florida Incontinence Scores (CCFISs) were noted. Patients were surveyed by using a telephone questionnaire to assess the quality of life and other outcome measures. Data were analysed using SPSS ver.19.0. Thirty patients (28 females and 2 males) with a median age of 67 years were included in the study. Of those patients, 37%, 50%, and 13% were noted to have passive, mixed and urge FI, respectively. Six of the patients (20%) had repeat Permacol injections, 5 of whom had sustained responses to the first Permacol injection for a mean of 11 months. There was a significant improvement in the CCFIS from a baseline median of 12.5, mean 12.8 interquartile range [IQR], 6-20), to a median of 3.5, mean 4.8 (IQR, 0-20), P < 0.001. Of the patients surveyed by telephone 89% were satisfied with their overall experience and the improvement in their symptoms following Permacol injections. This study has demonstrated that Permacol injection for the treatment of FI is safe and effective and has no associated major complications. However, the results are not permanent; consequently, a significant proportion of the patients with an initial response may require repeat injections.

Safety and Efficacy of Permacol Injection in the Treatment of Fecal Incontinence

PubMed Central

Ayers, Jennifer; Ayantunde, Abraham; Praveen, Bandipalyam V

2016-01-01

Purpose Permacol has been gaining popularity in recent times for the treatment of fecal incontinence (FI). This study aims to evaluate the safety and efficacy of anal submucosal Permacol injection in the treatment of FI. Methods All consecutive patients who underwent Permacol injection for FI over a 3-year period were included. Patients' data relating to obstetric history, anorectal/pelvic operations, type of FI, preoperative anorectal physiology results and follow-up details for outcome measures were collected. Preoperative and postoperative Cleveland Clinic Florida Incontinence Scores (CCFISs) were noted. Patients were surveyed by using a telephone questionnaire to assess the quality of life and other outcome measures. Data were analysed using SPSS ver.19.0. Results Thirty patients (28 females and 2 males) with a median age of 67 years were included in the study. Of those patients, 37%, 50%, and 13% were noted to have passive, mixed and urge FI, respectively. Six of the patients (20%) had repeat Permacol injections, 5 of whom had sustained responses to the first Permacol injection for a mean of 11 months. There was a significant improvement in the CCFIS from a baseline median of 12.5, mean 12.8 interquartile range [IQR], 6–20), to a median of 3.5, mean 4.8 (IQR, 0–20), P < 0.001. Of the patients surveyed by telephone 89% were satisfied with their overall experience and the improvement in their symptoms following Permacol injections. Conclusion This study has demonstrated that Permacol injection for the treatment of FI is safe and effective and has no associated major complications. However, the results are not permanent; consequently, a significant proportion of the patients with an initial response may require repeat injections. PMID:27218098

Does intrauterine injection of low-molecular-weight heparin improve the clinical pregnancy rate in intracytoplasmic sperm injection?

PubMed Central

El-Faissal, Yahia; Aboulghar, Mona; Mansour, Ragaa; Serour, Gamal I; Aboulghar, Mohamed

2016-01-01

Objective Heparin can modulate proteins, and influence processes involved in implantation and trophoblastic development. This study aimed to assess the improvement of clinical pregnancy and implantation rates after local intrauterine injection of low-molecular-weight heparin (LMWH) in patients undergoing intracytoplasmic sperm injection (ICSI). Methods A randomised case/control design was followed in women scheduled for ICSI. The study arm was injected with intrauterine LMWH during mock embryo transfer immediately following the ovum pickup procedure, while the control arm was given an intrauterine injection with a similar volume of tissue culture media. Side effects, the clinical pregnancy rate, and the implantation rate were recorded. Results The pregnancy rate was acceptable (33.9%) in the LMWH arm with no significant reported side effects, confirming the safety of the intervention. No statistically significant differences were found in the clinical pregnancy and implantation rates between both groups (p=0.182 and p=0.096, respectively). The odds ratio of being pregnant after intrauterine injection with LMWH compared to the control group was 0.572 (95% confidence interval [CI], 0.27−1.22), while the risk ratio was 0.717 (95% CI, 0.46−1.13; p=0.146). No statistical significance was found between the two groups in other factors affecting implantation, such as day of transfer (p=0.726), number of embryos transferred (p=0.362), or embryo quality. Conclusion Intrauterine injection of LMWH is a safe intervention, but the dose used in this study failed to improve the outcome of ICSI. Based on its safety, further research involving modification of the dosage and/or the timing of administration could result in improved ICSI success rates. PMID:28090465

Performance of a Fuel-Injection Spark-Ignition Engine Using a Hydrogenated Safety Fuel

NASA Technical Reports Server (NTRS)

Schey, Oscar W; Young, Alfred W

1934-01-01

This report presents the performance of a single-cylinder test engine using a hydrogenated safety fuel. The safety fuel has a flash point of 125 degrees f. (Cleveland open-dup method), which is high enough to remove most of the fire hazard, and an octane number of 95, which permits higher compression ratios to be used than are permissible with most undoped gasolines.

Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

PubMed

Verburg, M; Oldhoff, J M; Klemans, R J B; Lahey-de Boer, A; de Bruin-Weller, M S; Röckmann, H; Sanders, C; Bruijnzeel-Koomen, C A F M; Pasmans, S G M A; Knulst, A C

2015-11-01

Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

Driving reaction times in patients with foot and ankle pathology before and after image-guided injection: pain relief without improved function.

PubMed

Talusan, Paul G; Miller, Christopher P; Save, Ameya V; Reach, John S

2015-04-01

Foot and ankle pathology is common in the driving population. Local anesthetic steroid injections are frequent ambulatory treatments. Brake reaction time (BRT) has validated importance in motor vehicle safety. There are no prior studies examining the effect of foot and ankle pathology and injection treatment on the safe operation of motor vehicles. We studied BRT in patients with foot and ankle musculoskeletal disease before and after image-guided injection treatment. A total of 37 participants were enrolled. Image-guided injections of local anesthetic and steroid were placed into the pathological anatomical location of the right or left foot and ankles. A driving reaction timer was used to measure BRTs before and after injection. Patients suffering right "driving" and left "nondriving" pathology as well as a healthy control group were studied. All patients reported >90% pain relief postinjection. All injections were confirmed to be accurate by imaging. Post hoc Bonferonni analysis demonstrated significant difference between the healthy group and the right-sided injection group (P = .008). Mean BRT for healthy controls was 0.57 ± 0.11 s. Patients suffering right foot and ankle disease displayed surprisingly high BRTs (0.80 ± 0.23 s preinjection and 0.78 ± 0.16 s postinjection, P > .99). Left nondriving foot and ankle pathology presented a driving hazard as well (BRT of 0.75 ± 0.12 s preinjection and 0.77 ± 0.12 s postinjection, P > .99). Injections relieved pain but did not significantly alter BRT (P > .99 for all). Patients suffering chronic foot and ankle pathology involving either the driving or nondriving side have impaired BRTs. This preexisting driving impairment has not previously been reported and exceeds recommended cutoff safety values in the United States. Despite symptom improvement, there was no statistically significant change in BRT following image-guided injection in either foot and ankle. Therapeutic, Level II: Prospective Comparative Study. © 2014 The Author(s).

Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study.

PubMed

S Khouri, Albert; Huang, Grace; Y Huang, Linda

2017-01-01

To determine the safety and efficacy of intraoperative injection of mitomycin C (MMC) against conventional sponge-applied MMC during trabeculectomy. This study was a retrospective, comparative case series. Thirty eyes with primary open-angle glaucoma underwent consecutive trabeculectomies with MMC injection (injection group), and thirty eyes with sponge-applied MMC were as controls (sponge group). Data were collected preoperatively and postoperatively at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. Demographic data, applanation intraocular pressure (IOP), best-corrected visual acuity (VA), number of glaucoma medications, postoperative interventions, postoperative complications, and number of visits within 3 months were recorded. In order to stratify data, proportion of eyes achieving >30% IOP reduction from baseline with or without glaucoma medications was calculated and defined as surgical success. Mean IOP reduction at 1 year was significant in both the injection and sponge groups from baseline (46.8 and 37.8% respectively). The injection group had overall lower postoperative IOP and comparable complete treatment success, defined as achieving >30% IOP reduction without glaucoma medications (p = 0.941). The number of postoperative visits within 3 months and the proportion of eyes needing 5-fluorouracil (5-FU) intervention were significantly lower in the injection group (p = 0.03, p = 0.04 respectively). Injection of MMC was as safe and effective as sponge application with comparable estimated complete treatment success, less need for visits within 3 months, and 5-FU intervention. Surgeons may consider intraopera-tive injection of MMC in appropriate patient cohorts given comparable safety and efficacy and several advantages over traditional sponge application. Further study in a prospective, larger, long-term manner is necessary to assess this modality. How to cite this article: Khouri AS, Huang G, Huang LY. Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study. J Curr Glaucoma Pract 2017;11(3):101-106.

Feasibility Study for The Setting Up of a Safety System for Monitoring CO2 Storage at Prinos Field, Greece

NASA Astrophysics Data System (ADS)

Koukouzas, Nikolaos; Lymperopoulos, Panagiotis; Tasianas, Alexandros; Shariatipour, Seyed

2016-10-01

Geological storage of CO2 in subsurface geological structures can mitigate global warming. A comprehensive safety and monitoring system for CO2 storage has been undertaken for the Prinos hydrocarbon field, offshore northern Greece; a system which can prevent any possible leakage of CO2. This paper presents various monitoring strategies of CO2 subsurface movement in the Prinos reservoir, the results of a simulation of a CO2 leak through a well, an environmental risk assessment study related to the potential leakage of CO2 from the seafloor and an overall economic insight of the system. The results of the simulation of the CO2 leak have shown that CO2 reaches the seabed in the form of gas approximately 13.7 years, from the beginning of injection. From that point onwards the amount of CO2 reaching the seabed increases until it reaches a peak at around 32.9 years. During the injection period, the CO2 plume develops only within the reservoir. During the post-injection period, the CO2 reaches the seabed and develops side branches. These correspond to preferential lateral flow pathways of the CO2 and are more extensive for the dissolved CO2 than for the saturated CO2 gas. For the environmental risk assessment, we set up a model, using ArcGIS software, based on the use of data regarding the speeds of the winds and currents encountered in the region. We also made assumptions related to the flow rate of CO2. Results show that after a period of 10 days from the start of CO2 leakage the CO2 has reached halfway to the continental shores where the “Natura” protected areas are located. CO2 leakage modelling results show CO2 to be initially flowing along a preferential flow direction, which is towards the NE. However, 5 days after the start of leakage of CO2, the CO2 is also flowing towards the ENE. The consequences of a potential CO2 leak are considered spatially limited and the ecosystem is itself capable of recovering. We have tried to determine the costs necessary for the creation of such an integrated CO2 monitoring program both during the CO2 injection phase as well as during permanent storage. The most prevalent solution consists of purchasing both seismic equipment and Echosounder systems as well as privileging a monitoring system, which uses selected boreholes. The necessary period required for monitoring the study area is at least 20 years after the end of the CO2 storage period at Prinos. To the overall monitoring time, we should also add a further 20 years that are required for the injection phase as well as 12 years for the storage phase. The operating costs for monitoring the CO2 amount to 0,38 /ton CO2 and the total cost for EOR at Prinos amounts to 0,45 /ton CO2.

Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial.

PubMed

Kibuuka, Hannah; Berkowitz, Nina M; Millard, Monica; Enama, Mary E; Tindikahwa, Allan; Sekiziyivu, Arthur B; Costner, Pamela; Sitar, Sandra; Glover, Deline; Hu, Zonghui; Joshi, Gyan; Stanley, Daphne; Kunchai, Meghan; Eller, Leigh Anne; Bailer, Robert T; Koup, Richard A; Nabel, Gary J; Mascola, John R; Sullivan, Nancy J; Graham, Barney S; Roederer, Mario; Michael, Nelson L; Robb, Merlin L; Ledgerwood, Julie E

2015-04-18

Ebola virus and Marburg virus cause serious disease outbreaks with high case fatality rates. We aimed to assess the safety and immunogenicity of two investigational DNA vaccines, one (EBO vaccine) encoding Ebola virus Zaire and Sudan glycoproteins and one (MAR) encoding Marburg virus glycoprotein. RV 247 was a phase 1b, double-blinded, randomised, placebo-controlled clinical trial in Kampala, Uganda to examine the safety and immunogenicity of the EBO and MAR vaccines given individually and concomitantly. Healthy adult volunteers aged 18-50 years were randomly assigned (5:1) to receive three injections of vaccine or placebo at weeks 0, 4, and 8, with vaccine allocations divided equally between three active vaccine groups: EBO vaccine only, MAR vaccine only, and both vaccines. The primary study objective was to investigate the safety and tolerability of the vaccines, as assessed by local and systemic reactogenicity and adverse events. We also assessed immunogenicity on the basis of antibody responses (ELISA) and T-cell responses (ELISpot and intracellular cytokine staining assays) 4 weeks after the third injection. Participants and investigators were masked to group assignment. Analysis was based on the intention-to-treat principle. This trial is registered at ClinicalTrials.gov, number NCT00997607. 108 participants were enrolled into the study between Nov 2, 2009, and April 15, 2010. All 108 participants received at least one study injection (including 100 who completed the injection schedule) and were included in safety and tolerability analyses; 107 for whom data were available were included in the immunogenicity analyses. Study injections were well tolerated, with no significant differences in local or systemic reactions between groups. The vaccines elicited antibody and T-cell responses specific to the glycoproteins received and we detected no differences between the separate and concomitant use of the two vaccines. 17 of 30 (57%, 95% CI 37-75) participants in the EBO vaccine group had an antibody response to the Ebola Zaire glycoprotein, as did 14 of 30 (47%, 28-66) in the group that received both vaccines. 15 of 30 (50%, 31-69) participants in the EBO vaccine group had an antibody response to the Ebola Sudan glycoprotein, as did 15 of 30 (50%, 31-69) in the group that received both vaccines. Nine of 29 (31%, 15-51) participants in the MAR vaccine groups had an antibody response to the Marburg glycoprotein, as did seven of 30 (23%, 10-42) in the group that received both vaccines. 19 of 30 (63%, 44-80) participants in the EBO vaccine group had a T-cell response to the Ebola Zaire glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 13 of 30 (43%, 25-63) participants in the EBO vaccine group had a T-cell response to the Ebola Sudan glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 15 of 29 (52%, 33-71) participants in the MAR vaccine group had a T-cell response to the Marburg glycoprotein, as did 13 of 30 (43%, 25-63) in the group that received both vaccines. This study is the first Ebola or Marburg vaccine trial done in Africa, and the results show that, given separately or together, both vaccines were well tolerated and elicited antigen-specific humoral and cellular immune responses. These findings have contributed to the accelerated development of more potent Ebola virus vaccines that encode the same wild-type glycoprotein antigens as the EBO vaccine, which are being assessed during the 2014 Ebola virus disease outbreak in west Africa. US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparing (Semi-) Analytic Solutions Used to Model the Impact of Deep Carbon Injection on the Displacement and Pressurization of the Resident Brine

EPA Science Inventory

Injection of carbon dioxide into deep saline formations is seen as one possible technology for mitigating carbon emissions from utilities. The safety of the sequestered carbon dioxide is the focus of many studies with leakage through faults or abandoned wells as some of the main...

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome.

PubMed

Hazama, Shoichi; Nakamura, Yusuke; Takenouchi, Hiroko; Suzuki, Nobuaki; Tsunedomi, Ryouichi; Inoue, Yuka; Tokuhisa, Yoshihiro; Iizuka, Norio; Yoshino, Shigefumi; Takeda, Kazuyoshi; Shinozaki, Hirokazu; Kamiya, Akira; Furukawa, Hiroyuki; Oka, Masaaki

2014-03-10

To evaluate the safety of combination vaccine treatment of multiple peptides, phase I clinical trial was conducted for patients with advanced colorectal cancer using five novel HLA-A*2402-restricted peptides, three peptides derived from oncoantigens, ring finger protein 43 (RNF43), 34 kDa-translocase of the outer mitochondrial membrane (TOMM34), and insulin-like growth factor-II mRNA binding protein 3 (KOC1), and the remaining two from angiogenesis factors, vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. Eighteen HLA- A*2402-positive colorectal cancer patients who had failed to standard therapy were enrolled in this study. 0.5 mg, 1.0 mg or 3.0 mg each of the peptides was mixed with incomplete Freund's adjuvant and then subcutaneously injected at five separated sites once a week. We also examined possible effect of a single site injection of "the cocktail of 5 peptides" on the immunological responses. ELISPOT assay was performed before and after vaccinations in the schedule of every 4 weeks. The vaccine treatment using multiple peptides was well tolerated without any severe treatment-associated systemic adverse events. Dose-dependent induction of peptide-specific cytotoxic T lymphocytes was observed. The single injection of "peptides cocktail" did not diminish the immunological responses. Regarding the clinical outcome, one patient achieved complete response and 6 patients revealed stable disease for 4 to 7 months. The median overall survival time (MST) was 13.5 months. Patients, in which we detected induction of cytotoxic T lymphocytes specific to 3 or more peptides, revealed significantly better prognosis (MST; 27.8 months) than those with poorer immune responses (MST; 3.7 months) (p = 0.032). Our cancer vaccine treatment using multiple peptides is a promising approach for advanced colorectal cancer with the minimum risk of systemic adverse reactions. UMIN-CTR number UMIN000004948.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Dairy cow handling facilities and the perception of Beef Quality Assurance on Colorado dairies.

PubMed

Adams, A E; Olea-Popelka, F J; Grandin, T; Woerner, D R; Roman-Muniz, I N

2014-02-01

A survey was conducted on Colorado dairies to assess attitudes and practices regarding Dairy Beef Quality Assurance (DBQA). The objectives were to (1) assess the need for a new handling facility that would allow all injections to be administered via DBQA standards; (2) establish if Colorado dairy producers are concerned with DBQA; and (3) assess differences in responses between dairy owners and herdsmen. Of the 95 dairies contacted, 20 (21%) agreed to participate, with a median herd size of 1,178. When asked to rank the following 7 traits--efficiency, animal safety, human safety, ease of animal handling, ease of operation, inject per Beef Quality Assurance (BQA) procedures, and cost--in order of priority when designing a new handling facility, human and animal safety were ranked highest in priority (first or second) by the majority of participants, with ease of animal handling and efficiency ranked next. Interestingly, the administration of injections per BQA standards was ranked sixth or seventh by most participants. Respondents estimated the average annual income from the sale of cull cows to be 4.6% of all dairy income, with 50% receiving at least one carcass discount or condemnation in the past 12 mo. Although almost all of the participating dairy farmers stated that the preferred injection site for medications was the neck region, a significant number admitted to using alternate injection sites. In contrast, no difference was found between responses regarding the preferred and actual location for intravenous injections. Although most participating producers are aware of BQA injection guidelines, they perceive efficiency as more important, which could result in injections being administered in locations not promoted by BQA. Dairy owners and herdsmen disagreed in whether or not workers had been injured in the animal handling area in the last 12 mo. Handling facilities that allow for an efficient and safe way to administer drugs according to BQA guidelines and educational opportunities that highlight the effect of improved DBQA on profitability could prove useful. Dairy producers play a key role in ensuring that dairy beef is safe and high quality, and just as they are committed to producing safe and nutritious milk for their customers, they should be committed to producing the best quality beef. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple Dupuytren contractures.

PubMed

Coleman, Stephen; Gilpin, David; Kaplan, F Thomas D; Houston, Anthony; Kaufman, Gregory J; Cohen, Brian M; Jones, Nigel; Tursi, James P

2014-01-01

To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. In a multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success [flexion contracture 5° or less]) and adverse events were summarized. The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87° to 24° (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100° to 161°. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. Therapeutic IV. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Polymers for Improving the In Vivo Transduction Efficiency of AAV2 Vectors

PubMed Central

Moulay, Gilles; Boutin, Sylvie; Masurier, Carole; Scherman, Daniel; Kichler, Antoine

2010-01-01

Background Adeno-associated virus has attracted great attention as vehicle for body-wide gene delivery. However, for the successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is required. This not only raises questions about the technical feasibility of the large scale production but also about the overall safety of the approach. One way to overcome these problems would be to find strategies able to increase the in vivo efficiency. Methodology Here, we investigated whether polymers can act as adjuvants to increase the in vivo efficiency of AAV2. Our strategy consisted in the pre-injection of polymers before intravenous administration of mice with AAV2 encoding a murine secreted alkaline phosphatase (mSeAP). The transgene expression, vector biodistribution and tissue transduction were studied by quantification of the mSeAP protein and real time PCR. The injection of polyinosinic acid and polylysine resulted in an increase of plasmatic mSeAP of 2- and 12-fold, respectively. Interestingly, polyinosinic acid pre-injection significantly reduced the neutralizing antibody titer raised against AAV2. Conclusions Our results show that the pre-injection of polymers can improve the overall transduction efficiency of systemically administered AAV2 and reduce the humoral response against the capsid proteins. PMID:21203395

Intravitreal injection therapy in the treatment of noninfectious uveitis.

PubMed

Modorati, Giulio; Miserocchi, Elisabetta

2012-01-01

Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects. Copyright © 2012 S. Karger AG, Basel.

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability

PubMed Central

Bigaeva, Emilia; van Doorn, Eva; Liu, Heng; Hak, Eelko

2016-01-01

Background and Objectives QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. Methods A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Jadad scale was used to assess the study quality. Results Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04–6.24). No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10–15.35 and RR 2.55, 95% CI 1.41–4.59, respectively). ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08–10.97). Conclusions Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the relatively small number of individuals recruited in the included trials, especially in the control groups. PMID:27149269

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability.

PubMed

Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

2016-01-01

QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Jadad scale was used to assess the study quality. Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04-6.24). No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10-15.35 and RR 2.55, 95% CI 1.41-4.59, respectively). ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08-10.97). Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the relatively small number of individuals recruited in the included trials, especially in the control groups.

Recent developments in high altitude aircraft sampling - Mount St. Helens and stratospheric trace gases

NASA Astrophysics Data System (ADS)

Leifer, R.; Sommers, K. G.; Guggenheim, S. F.; Fisenne, I.

1981-02-01

An ultra-clean, low volume gas sampling system (CLASS), flown aboard a high altitude aircraft (WB-57F), and providing information on stratospheric trace gases is presented. Attention is given to the instrument design and the electronic control design. Since remote operation is mandatory on the WB-57F, a servo pressure transducer, electrical pressure switch for automatic shutdown, and a mechanical safety relief valve were installed on the sampling manifold, indicated on the CLASS flow chart. The electronic control system consists of hermetically sealed solid state timers, relays, and a stepping switch, for controlling the compressor pump and solenoid valves. In designing the automatic control system, vibration, shock, acceleration, extreme low temperature, and aircraft safety were important considerations. CLASS was tested on three separate occasions, and tables of analytical data from these flights are presented. Readiness capability was demonstrated when the Mount St. Helens eruption plume of May 18, 1980, was intercepted, and it was concluded that no large injection of Rn-222 entered the stratosphere or troposphere from the eruption.

Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges.

PubMed

Haque, Shadabul; Whittaker, Michael R; McIntosh, Michelle P; Pouton, Colin W; Kaminskas, Lisa M

2016-08-01

The inhaled delivery of nanomedicines can provide a novel, non-invasive therapeutic strategy for the more localised treatment of lung-resident diseases and potentially also enable the systemic delivery of therapeutics that are otherwise administered via injection alone. However, the clinical translation of inhalable nanomedicine is being hampered by our lack of understanding about their disposition and clearance from the lungs. This review provides a comprehensive overview of the biodegradable nanomaterials that are currently being explored as inhalable drug delivery systems and our current understanding of their disposition within, and clearance from the lungs. The safety of biodegradable nanomaterials in the lungs is discussed and latest updates are provided on the impact of inflammation on the pulmonary pharmacokinetics of inhaled nanomaterials. Overall, the review provides an in-depth and critical assessment of the lung clearance mechanisms for inhaled biodegradable nanomedicines and highlights the opportunities and challenges for their translation into the clinic. Copyright © 2016 Elsevier Inc. All rights reserved.

Mercury contamination study for flight system safety

NASA Technical Reports Server (NTRS)

Gorzynski, C. S., Jr.; Maycock, J. N.

1972-01-01

The effects and prevention of possible mercury pollution from the failure of solar electric propulsion spacecraft using mercury propellant were studied from tankage loading of post launch trajector injection. During preflight operations and initial flight mode there is little danger of mercury pollution if proper safety precautions are taken. Any spillage on the loading, mating, transportation, or launch pad areas is obvious and can be removed by vacuum cleaning soil and chemical fixing. Mercury spilled on Cape Kennedy ground soil will be chemically complexed and retained by the sandstone subsoil. A cover layer of sand or gravel on spilled mercury which has settled to the bottom of a water body adjacent to the system operation will control and eliminate the formation of toxic organic mercurials. Mercury released into the earth's atmosphere through leakage of a fireball will be diffused to low concentration levels. However, gas phase reactions of mercury with ozone could cause a local ozone depletion and result in serious ecological hazards.

Security attack detection algorithm for electric power gis system based on mobile application

NASA Astrophysics Data System (ADS)

Zhou, Chao; Feng, Renjun; Wang, Liming; Huang, Wei; Guo, Yajuan

2017-05-01

Electric power GIS is one of the key information technologies to satisfy the power grid construction in China, and widely used in power grid construction planning, weather, and power distribution management. The introduction of electric power GIS based on mobile applications is an effective extension of the geographic information system that has been widely used in the electric power industry. It provides reliable, cheap and sustainable power service for the country. The accurate state estimation is the important conditions to maintain the normal operation of the electric power GIS. Recent research has shown that attackers can inject the complex false data into the power system. The injection attack of this new type of false data (load integrity attack LIA) can successfully bypass the routine detection to achieve the purpose of attack, so that the control center will make a series of wrong decision. Eventually, leading to uneven distribution of power in the grid. In order to ensure the safety of the electric power GIS system based on mobile application, it is very important to analyze the attack mechanism and propose a new type of attack, and to study the corresponding detection method and prevention strategy in the environment of electric power GIS system based on mobile application.

Reactor Operations Monitoring System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, M.M.

1989-01-01

The Reactor Operations Monitoring System (ROMS) is a VME based, parallel processor data acquisition and safety action system designed by the Equipment Engineering Section and Reactor Engineering Department of the Savannah River Site. The ROMS will be analyzing over 8 million signal samples per minute. Sixty-eight microprocessors are used in the ROMS in order to achieve a real-time data analysis. The ROMS is composed of multiple computer subsystems. Four redundant computer subsystems monitor 600 temperatures with 2400 thermocouples. Two computer subsystems share the monitoring of 600 reactor coolant flows. Additional computer subsystems are dedicated to monitoring 400 signals from assortedmore » process sensors. Data from these computer subsystems are transferred to two redundant process display computer subsystems which present process information to reactor operators and to reactor control computers. The ROMS is also designed to carry out safety functions based on its analysis of process data. The safety functions include initiating a reactor scram (shutdown), the injection of neutron poison, and the loadshed of selected equipment. A complete development Reactor Operations Monitoring System has been built. It is located in the Program Development Center at the Savannah River Site and is currently being used by the Reactor Engineering Department in software development. The Equipment Engineering Section is designing and fabricating the process interface hardware. Upon proof of hardware and design concept, orders will be placed for the final five systems located in the three reactor areas, the reactor training simulator, and the hardware maintenance center.« less

Selective Gene Transfection of Individual Cells In Vitro with Plasmonic Nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina; Samaniego, Adam P.; Wen, Jianguo; Metelitsa, Leonid; Chang, Chung-Che; Lapotko, Dmitri

2011-01-01

Gene delivery and transfection of eukaryotic cells is widely used for research and for developing gene cell therapy. However, the existing methods lack selectivity, efficacy and safety when heterogeneous cell systems must be treated. We report a new method that employs plasmonic nanobubbles (PNBs) for delivery and transfection. A PNB is a novel, tunable cellular agent with a dual mechanical and optical action due to the formation of the vapor nanobubble around a transiently heated gold nanoparticle upon its exposure to a laser pulse. PNBs enabled the mechanical injection of the extracellular cDNA plasmid into the cytoplasm of individual target living cells, cultured leukemia cells and human CD34+CD117+ stem cells and expression of a green fluorescent protein (GFP) in those cells. PNB generation and lifetime correlated with the expression of green fluorescent protein in PNB-treated cells. Optical scattering by PNBs additionally provided the detection of the target cells and the guidance of cDNA injection at single cell level. In both cell models PNBs demonstrated a gene transfection effect in a single pulse treatment with high selectivity, efficacy and safety. Thus, PNBs provided targeted gene delivery at the single cell level in a single pulse procedure that can be used for safe and effective gene therapy. PMID:21315120

Selective gene transfection of individual cells in vitro with plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Samaniego, Adam P; Wen, Jianguo; Metelitsa, Leonid S; Chang, Chung-Che; Lapotko, Dmitri O

2011-06-10

Gene delivery and transfection of eukaryotic cells are widely used for research and for developing gene cell therapy. However, the existing methods lack selectivity, efficacy and safety when heterogeneous cell systems must be treated. We report a new method that employs plasmonic nanobubbles (PNBs) for delivery and transfection. A PNB is a novel, tunable cellular agent with a dual mechanical and optical action due to the formation of the vapor nanobubble around a transiently heated gold nanoparticle upon its exposure to a laser pulse. PNBs enabled the mechanical injection of the extracellular cDNA plasmid into the cytoplasm of individual target living cells, cultured leukemia cells and human CD34+ CD117+ stem cells and expression of a green fluorescent protein (GFP) in those cells. PNB generation and lifetime correlated with the expression of green fluorescent protein in PNB-treated cells. Optical scattering by PNBs additionally provided the detection of the target cells and the guidance of cDNA injection at single cell level. In both cell models PNBs demonstrated a gene transfection effect in a single pulse treatment with high selectivity, efficacy and safety. Thus, PNBs provided targeted gene delivery at the single cell level in a single pulse procedure that can be used for safe and effective gene therapy. Copyright © 2011 Elsevier B.V. All rights reserved.

Safety of a Trivalent Inactivated Influenza Vaccine in Health Care Workers in Kurdistan Province, Western Iran; A Longitudinal Follow-up Study.

PubMed

Soltani, Jafar; Jamil Amjadi, Mohamad

2014-03-01

We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines.

Safety of a Trivalent Inactivated Influenza Vaccine in Health Care Workers in Kurdistan Province, Western Iran; A Longitudinal Follow-up Study

PubMed Central

Soltani, Jafar; Jamil Amjadi, Mohamad

2014-01-01

We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines. PMID:24753646

Ultra-long-duration local anesthesia produced by injection of lecithin-coated methoxyflurane microdroplets.

PubMed

Haynes, D H; Kirkpatrick, A F

1985-11-01

This study was designed to evaluate a new drug delivery system. The authors undertook to determine if microdroplets prepared by encapsulating volatile anesthetics with a membrane of lecithin could be used for local anesthesia. Local anesthesia was determined by monitoring the response of the rat to tail clamping and electrical stimulation of the skin following the intradermal injection of the microdroplets. Microdroplets were prepared from isoflurane, enflurane, halothane, methoxyflurane, diethyl ether, chloroform, and heptane. Although all microdroplet preparations produced local anesthesia, only methoxyflurane microdroplets produced an ultra-long duration of local anesthesia (approximately 24 h). Further characterization of the methoxyflurane microdroplets revealed two important differences from conventional local anesthetics. First, the local anesthetic effect of methoxyflurane reached a plateau that did not change significantly for 20 h while the injection of lidocaine and bupivacaine resulted in a peak effect that returned to baseline within 1 and 3 h, respectively. Second, the anesthetic effect of methoxyflurane remained essentially localized to the site of injection, while the anesthetic effect of lidocaine and bupivacaine migrated 15 cm in less than 1 h. The toxicity and safety of methoxyflurane were evaluated. When administered over the dosage range 1-16% (v/v) intradermally, or by injections into muscle, or by repeat injections every 4 days for 16 days, all animals regained their pretreatment response to painful stimulations, and there was no evidence of gross injury to tissue. Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect. The present study demonstrates that methoxyflurane microdroplets produce an anesthetic effect that is highly localized, stable in intensity, ultra-long in duration, and reversible.

Safety of Repeated-Dose Intratympanic Injections with AM-101 in Acute Inner Ear Tinnitus.

PubMed

Staecker, Hinrich; Morelock, Michael; Kramer, Timothy; Chrbolka, Pavel; Ahn, Joong Ho; Meyer, Thomas

2017-09-01

Objective To evaluate the safety and tolerability of repeated intratympanic administration of the gel-formulated NMDA receptor antagonist AM-101 in acute patients with inner ear tinnitus. Study Design Prospective, double-blind, randomized, placebo-controlled study. Setting Sixty-nine secondary and tertiary sites in North America, Europe, and Asia. Subjects and Methods In total, 343 subjects with persistent acute tinnitus after traumatic cochlear injury or otitis media were randomized to receive 3 intratympanic doses of either AM-101 0.87 mg/mL or placebo over 3 to 5 days. They were followed for 84 days. The primary safety end point was the incidence of a clinically meaningful hearing deterioration from baseline to study day 35. Further safety assessments included tympanic membrane closure rates, analysis of adverse events, hematology, blood chemistry, and vital signs. In addition, data were collected on applied anesthetics and injection techniques. Results The treatment was well tolerated, with no intervention-related serious adverse events. The incidence of clinically meaningful hearing deterioration was low, comparable between treatment groups ( P = .82 for the primary safety end point) and not different between treated and untreated ears in unilaterally treated subjects. The rate of treatment and procedure-related adverse events was similar among treatment groups. The tympanic membrane was closed in 92% of subjects within 1 week and in all subjects by study day 84. Blood values and vital signs were inconspicuous. Conclusion Repeated intratympanic injections of AM-101 over a 3- to 5-day period appear to be safe and well tolerated, demonstrating the ability to potentially use this delivery approach over longer time periods.

Study of seed reprocessing systems for open cycle coal fired MHD power plants. Task 1: Selection of processes for more detailed study

NASA Astrophysics Data System (ADS)

1980-07-01

In most of the processes, a portion of the potassium seed material is converted to a compound not containing sulfur. The potassium in this form can, when injected upstream of the MHD channel, capture the sulfur released during the combustion of coal and eliminate the need for flue gas desulfurization equipment. Criteria considered in the evaluation included cost, state of development, seed loss, power requirements, availability, durability, key component risk, environmental impact, safety, controllability, and impurities buildup.

Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

PubMed

Wright, Jennifer G; Plikaytis, Brian D; Rose, Charles E; Parker, Scott D; Babcock, Janiine; Keitel, Wendy; El Sahly, Hana; Poland, Gregory A; Jacobson, Robert M; Keyserling, Harry L; Semenova, Vera A; Li, Han; Schiffer, Jarad; Dababneh, Hanan; Martin, Sandra K; Martin, Stacey W; Marano, Nina; Messonnier, Nancy E; Quinn, Conrad P

2014-02-12

We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months. A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response. Published by Elsevier Ltd.

Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

PubMed

Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

2015-04-01

To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

75 FR 48351 - Determination That DECA-DURABOLIN (Nandrolone Decanoate) Injection, 200 Milligrams/Milliliter, 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration... withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve... or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of...

Comparative study of the novel and conventional injection approach for inferior alveolar nerve block.

PubMed

Boonsiriseth, K; Sirintawat, N; Arunakul, K; Wongsirichat, N

2013-07-01

This study aimed to evaluate the efficacy of anesthesia obtained with a novel injection approach for inferior alveolar nerve block compared with the conventional injection approach. 40 patients in good health, randomly received each of two injection approaches of local anesthetic on each side of the mandible at two separate appointments. A sharp probe and an electric pulp tester were used to test anesthesia before injection, after injection when the patients' sensation changed, and 5 min after injection. This study comprised positive aspiration and intravascular injection 5% and neurovascular bundle injection 7.5% in the conventional inferior alveolar nerve block, but without occurrence in the novel injection approach. A visual analog scale (VAS) pain assessment was used during injection and surgery. The significance level used in the statistical analysis was p<0.05. For the novel injection approach compared with the conventional injection approach, no significant difference was found on the subjective onset, objective onset, operation time, duration of anesthesia and VAS pain score during operation, but the VAS pain score during injection was significantly different. The efficacy of inferior alveolar nerve block by the novel injection approach provided adequate anesthesia and caused less pain and greater safety during injection. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Detection of CO2 leakage by the surface-soil CO2-concentration monitoring (SCM) system in a small scale CO2 release test

NASA Astrophysics Data System (ADS)

Chae, Gitak; Yu, Soonyoung; Sung, Ki-Sung; Choi, Byoung-Young; Park, Jinyoung; Han, Raehee; Kim, Jeong-Chan; Park, Kwon Gyu

2015-04-01

Monitoring of CO2 release through the ground surface is essential to testify the safety of CO2 storage projects. We conducted a feasibility study of the multi-channel surface-soil CO2-concentration monitoring (SCM) system as a soil CO2 monitoring tool with a small scale injection. In the system, chambers are attached onto the ground surface, and NDIR sensors installed in each chamber detect CO2 in soil gas released through the soil surface. Before injection, the background CO2 concentrations were measured. They showed the distinct diurnal variation, and were positively related with relative humidity, but negatively with temperature. The negative relation of CO2 measurements with temperature and the low CO2 concentrations during the day imply that CO2 depends on respiration. The daily variation of CO2 concentrations was damped with precipitation, which can be explained by dissolution of CO2 and gas release out of pores through the ground surface with recharge. For the injection test, 4.2 kg of CO2 was injected 1 m below the ground for about 30 minutes. In result, CO2 concentrations increased in all five chambers, which were located less than 2.5 m of distance from an injection point. The Chamber 1, which is closest to the injection point, showed the largest increase of CO2 concentrations; while Chamber 2, 3, and 4 showed the peak which is 2 times higher than the average of background CO2. The CO2 concentrations increased back after decreasing from the peak around 4 hours after the injection ended in Chamber 2, 4, and 5, which indicated that CO2 concentrations seem to be recovered to the background around 4 hours after the injection ended. To determine the leakage, the data in Chamber 2 and 5, which had low increase rates in the CO2 injection test, were used for statistical analysis. The result shows that the coefficient of variation (CV) of CO2 measurements for 30 minutes is efficient to determine a leakage signal, with reflecting the abnormal change in CO2 concentrations. The CV of CO2 measurements for 30 minutes exceeded 5% about 5 minutes before the maximum CO2 concentration was detected. The contributions of this work are as follows: (1) SCM is an efficient monitoring tool to detect the CO2 release through the ground surface. (2) The statistical analysis method to determine the leakage and a monitoring frequency are provided, with analyzing background concentrations and CO2 increases in a small-scale injection test. (3) The 5% CV of CO2 measurements for 30 minutes can be used for the early warning in CO2 storage sites.

Dynamic dual-isotope molecular imaging elucidates principles for optimizing intrathecal drug delivery

PubMed Central

Wolf, Daniel A.; Hesterman, Jacob Y.; Sullivan, Jenna M.; Orcutt, Kelly D.; Silva, Matthew D.; Lobo, Merryl; Wellman, Tyler; Hoppin, Jack

2016-01-01

The intrathecal (IT) dosing route offers a seemingly obvious solution for delivering drugs directly to the central nervous system. However, gaps in understanding drug molecule behavior within the anatomically and kinetically unique environment of the mammalian IT space have impeded the establishment of pharmacokinetic principles for optimizing regional drug exposure along the neuraxis. Here, we have utilized high-resolution single-photon emission tomography with X-ray computed tomography to study the behavior of multiple molecular imaging tracers following an IT bolus injection, with supporting histology, autoradiography, block-face tomography, and MRI. Using simultaneous dual-isotope imaging, we demonstrate that the regional CNS tissue exposure of molecules with varying chemical properties is affected by IT space anatomy, cerebrospinal fluid (CSF) dynamics, CSF clearance routes, and the location and volume of the injected bolus. These imaging approaches can be used across species to optimize the safety and efficacy of IT drug therapy for neurological disorders. PMID:27699254

CFD Simulation of the distribution of ClO2 in fresh produce to improve safety

USDA-ARS?s Scientific Manuscript database

The shelf life of fresh-cut produce may be prolonged with the injection of bactericide gases like chlorine dioxide (ClO2). A comparative study has been conducted by modeling the injection of three different gases, CO2, ClO2 and N2 inside a PET clamshell containers commonly use to package fresh produ...

Office-based Electromyography-guided Botulinum Toxin Injection to the Cricopharyngeus Muscle: Optimal Patient Selection and Technique.

PubMed

Kim, Min-Su; Kim, Go-Woon; Rho, Young-Soo; Kwon, Kee-Hwan; Chung, Eun-Jae

2017-05-01

This retrospective study was carried out to investigate the effectiveness and safety of office-based electromyography-guided injection of botulinum toxin in the cricopharyngeus muscle of patients who did not show upper esophageal sphincter passage in a swallowing study in spite of maximal swallowing rehabilitation. Thirty-six patients who showed no or limited ability to oral feed after maximum swallowing rehabilitation were enrolled. Video fluoroscopic swallowing study, flexible endoscopic evaluation of swallowing, disability rating scale, penetration aspiration score, and National Institutes of Health swallowing safety scale were used in the evaluation of dysphagia. Success was defined as nondependence on gastrostomy for patients who previously were dependent on gastrostomy and improvement in disability rating scale score after botulinum toxin injections. The total success rate was 63.9%. The complication rate was very low, with only 1 patient showing temporary unilateral vocal fold paralysis. Botulinum toxin injection was more effective in patients with cranial nerve IX or X palsy than in those without it ( P = .006). This procedure can be a simple, safe, and effective tool in patients with cricopharyngeal dysfunction after swallowing rehabilitation, especially for cranial nerve IX or X palsy.

Trial of a novel endoscopic tattooing biopsy forceps on animal model

PubMed Central

Si, Jian-Min; Sun, Lei-Min; Fan, Yu-Jing; Wang, Liang-Jing

2005-01-01

AIM: To tattoo gastric mucosa with a novel medical device which could be used to monitor and follow-up gastric mucosal lesions. METHODS: Combining endoscopic biopsy with sclerotherapy injection, we designed a new device that could perform biopsy and injection simultaneously. We performed endoscopies on a pig by using a novel endoscope tattoo biopsy forceps for 15 mo. At the same time, we used two-step method combining sclerotherapy injection needle with endoscopic biopsy. The acuity, inflammation and duration of endoscopy were compared between two methods. RESULTS: Compared with the old two-step method, although the inflammation induced by our new device was similar, the duration of procedure was markedly decreased and the acuity of tattooing was better than the old two-step method. All characteristics of the novel device complied with national safety guidelines. Follow-up gastroscopy after 15 mo showed the stained site with injection of 1:100 0.5 mL of India ink was still markedly visible with little inflammatory reaction. CONCLUSION: Endoscopic tattooing biopsy forceps can be widely used in monitoring precancerous lesions. Its safety and effectiveness has been established in animals. PMID:15793881

Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study.

PubMed

Sundy, John S; Schumacher, H Ralph; Kivitz, Alan; Weinstein, Steven P; Wu, Richard; King-Davis, Shirletta; Evans, Robert R

2014-08-01

To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT). This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint. Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p < 0.0001), fewer patients with ≥ 1 and ≥ 2 gout flares (p < 0.0001), and 64.9% fewer gout flare days (p < 0.0001) relative to placebo. Weekly subcutaneous administration of rilonacept 160 mg showed no new safety signals. The safety profile was consistent with previous studies. Rilonacept also significantly reduced the risk of gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials

PubMed Central

Koh, Kim Hwee

2016-01-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. PMID:27570870

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials.

PubMed

Koh, Kim Hwee

2016-12-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. Copyright: © Singapore Medical Association.

Safety of available and emerging drug therapies for hyperhidrosis.

PubMed

Hosp, Christine; Hamm, Henning

2017-09-01

Hyperhidrosis affects 4.8% of the U.S. population and has been underestimated by physicians for long time despite considerable interference with quality of life. Many patients suffer from primary (idiopathic) hyperhidrosis which results from over-activity of sympathetic nerves and is restricted to specific body areas, mostly the axillae, palms, soles, or head. Secondary hyperhidrosis is caused by an underlying disease or the intake of medications and often involves large parts of the body. Numerous effective therapies with topical or systemic drugs and surgical options are available. Areas covered: Efficacy and safety data on aluminum salts, anticholinergic drugs for topical or systemic application, and on intradermal botulinum toxin injections used to treat hyperhidrosis are critically evaluated, including data from clinical trials with focus on possible side effects and long-term complications in dispute. Expert opinion: Hyperhidrosis often responds well to available therapies. Depending on the type of hyperhidrosis treatment should be topical/local or systemic. Most of the side effects are mild, transient and easily manageable. In case of systemic treatment with anticholinergics low dosing and up-titration of medication is necessary to avoid severe adverse effects. Concerns about the promotion of breast cancer and Alzheimer disease by topical aluminum salts are unsolved.

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

PubMed

Greenberg, David P; Robertson, Corwin A; Noss, Michael J; Blatter, Mark M; Biedenbender, Rex; Decker, Michael D

2013-01-21

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages. Copyright © 2012 Elsevier Ltd. All rights reserved.

Technical tips for collagenase injection treatment for Dupuytren contracture.

PubMed

Meals, Roy A; Hentz, Vincent R

2014-06-01

We describe technical tips for injecting collagenase into Dupuytren cords based on experience acquired during the prerelease Food and Drug Administration clinical trials and with subsequent clinical practice. These tips include techniques for extracting the reconstituted enzyme efficiently from the vial, injecting the cord(s) with increased safety to the tendons, and anesthetizing the hand before manipulation. The tips are intended to supplement but by no means replace the manufacturer's prescribing information and training video. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Ultrabroadband photonic internet: safety aspects

NASA Astrophysics Data System (ADS)

Kalicki, Arkadiusz; Romaniuk, Ryszard

2008-11-01

Web applications became most popular medium in the Internet. Popularity, easiness of web application frameworks together with careless development results in high number of vulnerabilities and attacks. There are several types of attacks possible because of improper input validation. SQL injection is ability to execute arbitrary SQL queries in a database through an existing application. Cross-site scripting is the vulnerability which allows malicious web users to inject code into the web pages viewed by other users. Cross-Site Request Forgery (CSRF) is an attack that tricks the victim into loading a page that contains malicious request. Web spam in blogs. There are several techniques to mitigate attacks. Most important are web application strong design, correct input validation, defined data types for each field and parameterized statements in SQL queries. Server hardening with firewall, modern security policies systems and safe web framework interpreter configuration are essential. It is advised to keep proper security level on client side, keep updated software and install personal web firewalls or IDS/IPS systems. Good habits are logging out from services just after finishing work and using even separate web browser for most important sites, like e-banking.

Clinical application of indocyanine green-fluorescence imaging during hepatectomy

PubMed Central

Ishizawa, Takeaki; Saiura, Akio

2016-01-01

In hepatobiliary surgery, the fluorescence and bile excretion of indocyanine green (ICG) can be used for real-time visualization of biological structure. Fluorescence cholangiography is used to obtain fluorescence images of the bile ducts following intrabiliary injection of 0.025−0.5 mg/mL ICG or intravenous injection of 2.5 mg ICG. Recently, the latter technique has been used in laparoscopic/robotic cholecystectomy. Intraoperative fluorescence imaging can be used to identify subcapsular hepatic tumors. Primary and secondary hepatic malignancy can be identified by intraoperative fluorescence imaging using preoperative intravenous injection of ICG through biliary excretion disorders that exist in cancerous tissues of hepatocellular carcinoma (HCC) and in non-cancerous hepatic parenchyma around adenocarcinoma foci. Intraoperative fluorescence imaging may help detect tumors to be removed, especially during laparoscopic hepatectomy, in which visual inspection and palpation are limited, compared with open surgery. Fluorescence imaging can also be used to identify hepatic segments. Boundaries of hepatic segments can be visualized following injection of 0.25−2.5 mg/mL ICG into the portal veins or by intravenous injection of 2.5 mg ICG following closure of the proximal portal pedicle toward hepatic regions to be removed. These techniques enable identification of hepatic segments before hepatectomy and during parenchymal transection for anatomic resection. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool that can enhance the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. PMID:27500144

Modeling of a sensitive time-of-flight flash LiDAR system

NASA Astrophysics Data System (ADS)

Fathipour, V.; Wheaton, S.; Johnson, W. E.; Mohseni, H.

2016-09-01

used for monitoring and profiling structures, range, velocity, vibration, and air turbulence. Remote sensing in the IR region has several advantages over the visible region, including higher transmitter energy while maintaining eye-safety requirements. Electron-injection detectors are a new class of detectors with high internal avalanche-free amplification together with an excess-noise-factor of unity. They have a cutoff wavelength of 1700 nm. Furthermore, they have an extremely low jitter. The detector operates in linear-mode and requires only bias voltage of a few volts. This together with the feedback stabilized gain mechanism, makes formation of large-format high pixel density electron-injection FPAs less challenging compared to other detector technologies such as avalanche photodetectors. These characteristics make electron-injection detectors an ideal choice for flash LiDAR application with mm scale resolution at longer ranges. Based on our experimentally measured device characteristics, a detailed theoretical LiDAR model was developed. In this model we compare the performance of the electron-injection detector with commercially available linear-mode InGaAs APD from (Hamamatsu G8931-20) as well as a p-i-n diode (Hamamatsu 11193 p-i-n). Flash LiDAR images obtained by our model, show the electron-injection detector array (of 100 x 100 element) achieves better resolution with higher signal-to-noise compared with both the InGaAs APD and the p-i-n array (of 100 x 100 element).

[A Phase 1 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP)].

PubMed

Torizuka, K; Yonekura, Y; Nishimura, T; Tamaki, N; Uehara, T; Ikekubo, K; Hino, M

1991-07-01

Phase 1 study of beta-methyl-p-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), a new radiopharmaceutical developed for the evaluation of myocardial fatty acid metabolism, was performed in six normal volunteers to evaluate its biodistribution and safety. After intravenous injection of 111 MBq of 123I-BMIPP, the agent accumulated to the myocardium rapidly (5.4 +/- 0.6% at 1.5 hr after injection) and was washed-out slowly (5.1 +/- 0.4% at 3.0hr). 123I-BMIPP demonstrated no significant accumulation to any specific organs other than myocardium, liver and muscle. Myocardium was clearly visualized in the planar and SPECT images obtained 30 min and 3 hrs after injection. The absorption doses from 123I-BMIPP estimated by MIRD method were lower than those from 201Tl in all organs. Neither adverse reactions nor abnormal clinical laboratory findings were found in the safety evaluation. These results suggest 123I-BMIPP is a promising agent for evaluating myocardial fatty acid metabolism.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

PubMed

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor

PubMed Central

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M.; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G.; Scholler, John; Levine, Bruce L.; Albelda, Steven M.; June, Carl H.

2010-01-01

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CARs). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week post electroporation. Multiple injections of RNA CAR electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(−/−) mice. Dramatic tumor reduction also occurred when the pre-existing intraperitoneal human-derived tumors, that had been growing in vivo for over 50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes demonstrating that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. PMID:20926399

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

PubMed

Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

2016-09-01

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Large-particle calcium hydroxylapatite injection for correction of facial wrinkles and depressions.

PubMed

Alam, Murad; Havey, Jillian; Pace, Natalie; Pongprutthipan, Marisa; Yoo, Simon

2011-07-01

Small-particle calcium hydroxylapatite (Radiesse, Merz, Frankfurt, Germany) is safe and effective for facial wrinkle reduction, and has medium-term persistence for this indication. There is patient demand for similar fillers that may be longer lasting. We sought to assess the safety and persistence of effect in vivo associated with use of large-particle calcium hydroxylapatite (Coaptite, Merz) for facial augmentation and wrinkle reduction. This was a case series of 3 patients injected with large-particle calcium hydroxylapatite. Large-particle calcium hydroxylapatite appears to be effective and well tolerated for correction of facial depressions, including upper mid-cheek atrophy, nasolabial creases, and HIV-associated lipoatrophy. Adverse events included erythema and edema, and transient visibility of the injection sites. Treated patients, all of whom had received small-particle calcium hydroxylapatite correction before, noted improved persistence at 6 and 15 months with the large-particle injections as compared with prior small-particle injections. This is a small case series, and there was no direct control to compare the persistence of small-particle versus large-particle correction. For facial wrinkle correction, large-particle calcium hydroxylapatite has a safety profile comparable with that of small-particle calcium hydroxylapatite. The large-particle variant may have longer persistence that may be useful in selected clinical circumstances. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

PubMed

Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

2017-03-01

Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

Industrial-grade silicone injections causing intermittent bilateral malar swelling: review of safety and efficacy of techniques and products available.

PubMed

Seward, Austin C; Meara, Daniel J

2013-07-01

Silicone and other fillers have become a popular aid to increase soft tissue density, decrease static skin rhytids, and treat muscle wasting, particularly in the face. As a result, injectable silicone has become popular in patients with the human immunodeficiency virus (HIV). It has been postulated that highly active antiretroviral therapy detrimentally induces the physiologic process of fat atrophy of the temporal and buccal fat pads of the face and regional fat wasting of the arms, legs, and buttocks and that HIV protease inhibitors may induce fat atrophy by binding and inhibiting homologous human proteins that are involved in fat metabolism. The classic hollowed-out facial appearance linked to HIV positivity can have detrimental social implications in infected patients who are otherwise very functional. In consequence, facial implantation, fat transplantation, and dermal and subcutaneous fillers have been used to aid in the restoration of facial appearance. This report describes the case of a patient who underwent multiple rounds of silicone injections and complained of intermittent facial swelling and pain long after the injections. The authors report on the safety of specific medical-grade injectable fillers and techniques found to be safely effective, especially in the HIV-positive population. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

High-Intensity Radiated Field Fault-Injection Experiment for a Fault-Tolerant Distributed Communication System

NASA Technical Reports Server (NTRS)

Yates, Amy M.; Torres-Pomales, Wilfredo; Malekpour, Mahyar R.; Gonzalez, Oscar R.; Gray, W. Steven

2010-01-01

Safety-critical distributed flight control systems require robustness in the presence of faults. In general, these systems consist of a number of input/output (I/O) and computation nodes interacting through a fault-tolerant data communication system. The communication system transfers sensor data and control commands and can handle most faults under typical operating conditions. However, the performance of the closed-loop system can be adversely affected as a result of operating in harsh environments. In particular, High-Intensity Radiated Field (HIRF) environments have the potential to cause random fault manifestations in individual avionic components and to generate simultaneous system-wide communication faults that overwhelm existing fault management mechanisms. This paper presents the design of an experiment conducted at the NASA Langley Research Center's HIRF Laboratory to statistically characterize the faults that a HIRF environment can trigger on a single node of a distributed flight control system.

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

PubMed Central

Xie, Z; Chen, F; Wu, X; Zhuang, C; Zhu, J; Wang, J; Ji, H; Wang, Y; Hua, X

2012-01-01

Purpose To elucidate the safety and efficacy of exogenous erythropoietin (EPO) for the protection of photoreceptor cells in a rat model of retinal detachment (RD). Methods Recombinant rat EPO (400 ng) was injected into the vitreous cavity of normal rats to observe the eye manifestations. Retinal function was assessed by flash electroretinograms. Histopathological examination of retinal tissue was performed at 14 days and 2 months after injection, respectively. To investigate the inhibitory effect of EPO on photoreceptor cell apoptosis in RD rats, 100, 200, or 400 ng EPO was injected into the vitreous cavity immediately after RD model establishment. Apoptosis of photoreceptor cells was determined at 3 days after injection. Caspase-3 activation was measured by western blot analysis and immunofluorescence, respectively, and the level of Bcl-XL expression was analyzed by western blot. Results Intravitreal injection of EPO 400 ng into normal rats had no significant impact on retinal function, morphology, or structure. Apoptosis of retinal photoreceptor cells apparently increased after RD and was significantly reduced following EPO treatment. The thickness of the outer nuclear layer in the RD+400 ng group was significantly thicker than that in other experimental RD groups both at 14 days and at 2 months after RD (P<0.05). Western blot and immunofluorescence analyses showed decreased caspase-3 activation and increased Bcl-XL expression following EPO treatment. Conclusion Intravitreal injection of EPO 400 ng is safe, and EPO may suppress caspase-3 activation and enhance Bcl-XL expression, resulting in inhibition of apoptosis and protection of photoreceptor cells. PMID:22020175

Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson's disease.

PubMed

Triadafilopoulos, George; Gandhy, Rita; Barlow, Carrolee

2017-11-01

Gastrointestinal symptoms, such as dysphagia, postprandial bloating, and defecatory straining are common in Parkinson's Disease (PD) and they impact quality of life. Endoscopic botulinum neurotoxin (BoNT) injection has been used in the treatment of dysphagia, gastroparesis and chronic anismus. To examine the feasibility, safety and efficacy of endoscopically delivered BoNT injection to distal esophagus, pylorus or anal canal aiming at relieving regional gastrointestinal symptoms in patients with PD. This is a retrospective open cohort pilot study to assess the clinical response to endoscopic BoNT injection on selected PD patients with symptoms and identifiable abnormalities on high-resolution manometry and wireless motility capsule, to generate early uncontrolled data on feasibility, tolerability, safety and efficacy. Baseline symptoms and response to therapy were assessed by questionnaires. Fourteen PD patients (10 M:4 F), mean age 73 (range: 62-93) were treated. Three patients had esophageal Botox for ineffective esophageal motility (IEM) (n = 1), esophago-gastric junction outlet obstruction (EGJOO) & IEM (n = 1), and diffuse esophageal spasm (DES) (n = 1). Nine patients were treated with pyloric BoNT injection for gastroparesis with mean gastric transit time of 21.2 h; range 5.2-44.2 h. Two patients received anal Botox for defecatory dyssynergia ((Type I) (n = 1) and overlap (slow-transit and dyssynergic) constipation (n = 1). Endoscopic BoNT injection (100-200 units) was well tolerated and there were no significant adverse events. Endoscopic BoNT injection to esophagus, pylorus or anal canal is safe, well-tolerated and leads to symptomatic improvement that lasts up to several months. The procedure can be repeated as needed and combined with other therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heparin pharmacovigilance in Brazil.

PubMed

Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

2011-01-01

To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

Oxygen sensor signal validation for the safety of the rebreather diver.

PubMed

Sieber, Arne; L'abbate, Antonio; Bedini, Remo

2009-03-01

In electronically controlled, closed-circuit rebreather diving systems, the partial pressure of oxygen inside the breathing loop is controlled with three oxygen sensors, a microcontroller and a solenoid valve - critical components that may fail. State-of-the-art detection of sensor failure, based on a voting algorithm, may fail under circumstances where two or more sensors show the same but incorrect values. The present paper details a novel rebreather controller that offers true sensor-signal validation, thus allowing efficient and reliable detection of sensor failure. The core components of this validation system are two additional solenoids, which allow an injection of oxygen or diluent gas directly across the sensor membrane.

76 FR 78669 - Determination that Bretylium Tosylate Injection, 50 Milligrams/Milliliter, Was Not Withdrawn From...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...)/milliliter (mL), was not withdrawn from sale for reasons of safety or effectiveness. This determination will... or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of...

78 FR 17933 - Determination That BENADRYL (diphenhydramine hydrochloride) Injection and Two Other Drug Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated... withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA...

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.

PubMed

Overton, Edgar Turner; Lawrence, Steven J; Wagner, Eva; Nopora, Katrin; Rösch, Siegfried; Young, Philip; Schmidt, Darja; Kreusel, Christian; De Carli, Sonja; Meyer, Thomas P; Weidenthaler, Heinz; Samy, Nathaly; Chaplin, Paul

2018-01-01

Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts. The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637. Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment. The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA. ClinicalTrials.gov NCT01144637.

Density of Gadolinium Nitrate Solutions for the High Flux Isotope Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Paul Allen; Lee, Denise L

2009-05-01

In late 1992, the High Flux Isotope Reactor (HFIR) was planning to switch the solution contained in the poison injection tank from cadmium nitrate to gadolinium nitrate. The poison injection system is an emergency system used to shut down the reactor by adding a neutron poison to the cooling water. This system must be able to supply a minimum of 69 pounds of gadolinium to the reactor coolant system in order to guarantee that the reactor would become subcritical. A graph of the density of gadolinium nitrate solutions over a concentration range of 5 to 30 wt% and a temperaturemore » range of 15 to 40{sup o}C was prepared. Routine density measurements of the solution in the poison injection tank are made by HFIR personnel, and an adaptation of the original graph is used to determine the gadolinium nitrate concentration. In late 2008, HFIR personnel decided that the heat tracing that was present on the piping for the poison injection system could be removed without any danger of freezing the solution; however, the gadolinium nitrate solution might get as cold as 5{sup o}C. This was outside the range of the current density-concentration correlation, so the range needed to be expanded. This report supplies a new density-concentration correlation that covers the extended temperature range. The correlation is given in new units, which greatly simplifies the calculation that is required to determine the pounds of gadolinium in the tank solution. The procedure for calculating the amount of gadolinium in the HFIR poison injection system is as follows: (1) Calculate the usable volume in the system; (2) Measure the density of the solution; (3) Calculate the gadolinium concentration using the following equation: Gd(lb/ft{sup 3}) = measured density (g/mL) x 34.681 - 34.785; (4) Calculate the amount of gadolinium in the system using the following equation: Amount of Gd(lb) = Gd concentration (lb/ft{sup 3}) x usable volume (ft{sup 3}). The equation in step 3 is exact for a temperature of 5{sup o}C, and overestimates the gadolinium concentration at all higher temperatures. This guarantees that the calculation is conservative, in that the actual concentration will be at least as high as that calculated. If an additional safety factor is desired, it is recommended that an administrative control limit be set that is higher than the required minimum amount of gadolinium.« less

Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit.

PubMed

Papangkorn, Kongnara; Prendergast, Eri; Higuchi, John W; Brar, Balbir; Higuchi, William I

2017-12-01

To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology. The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response. All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

Administering Multiple Injectable Vaccines During a Single Visit-Summary of Findings From the Accelerated Introduction of Inactivated Polio Vaccine Globally.

PubMed

Dolan, Samantha B; Patel, Manish; Hampton, Lee M; Burnett, Eleanor; Ehlman, Daniel C; Garon, Julie; Cloessner, Emily; Chmielewski, Elizabeth; Hyde, Terri B; Mantel, Carsten; Wallace, Aaron S

2017-07-01

In 2013, the World Health Organization's (WHO's) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, "multiple injections") during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children's Fund data from 2013-2015 were used to assess multiple-injection visits included in national immunization schedules. Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was largely from developed countries. Parental acceptance of multiple injections was associated with a positive provider recommendation to the caregiver. Findings of the systematic review identified that the intramuscular route is preferred over the subcutaneous route for vaccine administration and that the vastus lateralis muscle is preferred over the deltoid muscle for intramuscular injections. Recommendations on vaccine spacing and procedural preparedness were based on practical necessities, but comparative evidence was not identified. During 2013-2015, 85 countries added IPV to their immunization schedules, 46 (55%) of which adopted a schedule resulting in 3 injectable vaccines being administered in a single visit. The multiple-injection experience identified gaps in guidance for future vaccine introductions. Global partner organizations quickly mobilized to assess, document, and communicate the existing global experience on multiple-injection visits. This evidence-based approach provided reassurance to opinion leaders, health workers, and professional societies, thus encouraging uptake of IPV as a second or third injection in an accelerated manner globally. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis.

PubMed

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. ClinicalTrials.gov (NCT02343003).

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis

PubMed Central

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Background and Objectives Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. Methods This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. Results There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. Conclusions This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. Clinical Trial Registration: ClinicalTrials.gov (NCT02343003). PMID:29095245

Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: comparison of safety, reactogenicity, and immunogenicity.

PubMed

Reisinger, Keith S; Block, Stanley L; Izu, Allen; Groth, Nicola; Holmes, Sandra J

2009-09-15

This study assessed the safety, reactogenicity, and immunogenicity of an injectable cell culture-derived influenza vaccine (CCIV), compared with those of an injectable egg-based trivalent inactivated influenza vaccine (TIV). Adult subjects (n = 613; 18 to <50 years of age) were randomized (1:1) to receive either CCIV or TIV. The safety and reactogenicity of the 2 vaccines were assessed on the basis of solicited indicators and other adverse events (AEs) within 7 days of vaccination. All serious AEs and those AEs resulting in withdrawal were recorded throughout the study. Antibody titers were determined by the hemagglutination inhibition assay, using egg- and cell-derived antigens. Immunogenicity was assessed on the basis of the ratio of postvaccination (day 22) geometric mean titers (GMTs) between the 2 vaccines, seroprotection rates, and seroconversion rates. There was no clinically relevant difference between the safety and reactogenicity profiles of the 2 vaccines. The immunogenicity of CCIV was demonstrated to be noninferior to that of TIV on the basis of the ratio of postvaccination GMTs between the 2 vaccines. GMTs, seroprotection rates, and seroconversion rates were comparable between the 2 vaccines. The safety, reactogenicity, and immunogenicity of the CCIV and the egg-based TIV are comparable.

Development of New Laser Protective Dyes. Phase 2.

DTIC Science & Technology

DYE LASERS, PROTECTION, LASERS, DYES , HAZARDS, SYNTHESIS, EYE SAFETY, OPTICAL MATERIALS, PLASTICS, LENSES, THERMAL STABILITY, CYANINE DYES , POLYCARBONATES, INJECTION MOLDING, NEAR INFRARED RADIATION, FLUORENES.

The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial.

PubMed

Chiu, C K; Low, T H; Tey, Y S; Singh, V A; Shong, H K

2011-12-01

Chronic, nonspecific low back pain is a difficult ailment to treat and poses an economic burden in terms of medical expenses and productivity loss. The aim of this study was to determine the efficacy and safety of intramuscular metylcobalamin in the treatment of chronic nonspecific low back pain. This was a double-blinded, randomised, controlled experimental study. 60 patients were assigned to either the methylcobalamin group or the placebo group. The former received intramuscular injections of 500 mcg parenteral methylcobalamin in 1 ml solution three times a week for two weeks, and the placebo group received 1 ml normal saline. Patients were assessed with Oswestry Disability Index questionnaire Version 2.0 and Visual Analogue Scale pain score. They were scored before commencement of the injections and at two months interval. Of the 60 patients, 27 received the placebo injections and 33 were given methylcobalamin injections. A total of 58 patients were available for review at two months (placebo: n is 26; methylcobalamin: n is 32). There was a significant improvement in the Oswestry Disability Index and Visual Analogue Scale pain scores in the methylcobalamin group as compared with the placebo group (p-value less than 0.05). Only minor adverse reactions such as pain and haematoma at the injection sites were reported by some patients. Intramuscular methylcobalamin is both an effective and safe method of treatment for patients with nonspecific low back pain, both singly or in combination with other forms of treatment.

Treatment of Recurrent Dupuytren Contracture in Joints Previously Effectively Treated With Collagenase Clostridium histolyticum.

PubMed

Bear, Brian J; Peimer, Clayton A; Kaplan, F Thomas D; Kaufman, Gregory J; Tursi, James P; Smith, Ted

2017-05-01

Collagenase Clostridium histolyticum (CCH) is approved for the treatment of adults with Dupuytren contracture with a palpable cord. This open-label, phase 4 study evaluated the safety and efficacy of CCH for the retreatment of recurrent contractures in joints that were previously effectively treated with CCH. Patients participating in a long-term follow-up study who had contracture recurrence (increased ≥ 20° with a palpable cord) after successful treatment in the previous study were eligible. Recurrent joint contractures were treated with up to 3 CCH injections (∼ 1 month apart). Patients were followed for 1 year to evaluate safety. Assessments included change in joint contracture, range of motion, and the percentage of joints that achieved contracture of 5° or less at day 30 after the last injection. The efficacy analysis included 51 patients with 1 treated joint per patient (31 metacarpophalangeal, 20 proximal interphalangeal). A total of 35 joints (69%) received 1 injection, 12 (24%) received 2 injections, and 4 (8%) received 3 injections. Fifty-seven percent of joints achieved contracture of 5° or less (29 of 51). Overall, 86% (43 of 50) patients had a 20° or greater increase in range of motion. The adverse event profile was consistent with previous studies. One ligament injury was reported. At a short-term follow-up of 1 year, recurrent contracture in joints previously successfully treated with CCH may be effectively retreated with up to 3 injections of CCH. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Multiple collagenase injections are safe for treatment of Dupuytren's contractures.

PubMed

Gajendran, Varun K; Hentz, Vincent; Kenney, Deborah; Curtin, Catherine M

2014-07-01

The authors report the case of a 65-year-old, right-hand-dominant man who had severe Dupuytren's disease with multiple cords and flexion contractures of the metacarpophalangeal and proximal interphalangeal joints of both hands and underwent repeated collagenase injections for treatment. Collagenase has been shown to be safe and effective in the treatment of Dupuytren's contractures when administered as a single dose, but the results of multiple injections over a prolonged period are unknown. Antibodies to collagenase develop in all patients after several treatments, raising concerns about safety and efficacy as a result of sensitization from repeated exposures. The antibodies generated as a result of repeated exposure to collagenase could theoretically render it less effective with time and could also lead to immune reactions as severe as anaphylaxis. The authors present the case of a single patient who experienced continued correction of his contractures with only minor and self-limited adverse reactions after administration of 12 collagenase doses through 15 injections during a 4-year period. Over time, the injections continued to be effective at correcting metacarpophalangeal joint contractures, but less effective at correcting proximal interphalangeal joint contractures. The patient did eventually require a fasciectomy, but the safety and modest success of the repeated collagenase injections shows promise for a less invasive treatment with a better risk profile than open fasciectomy. Although further studies are needed, repeated administration of collagenase appears to be safe and modestly effective for severe Dupuytren's contractures, although a fasciectomy may ultimately be required in the most severe cases. Copyright 2014, SLACK Incorporated.

Salvianolate injection in the treatment of unstable angina pectoris

PubMed Central

Zhang, Dan; Wu, Jiarui; Liu, Shi; Zhang, Xiaomeng; Zhang, Bing

2016-01-01

Abstract Background: To systematically evaluate the clinical efficacy and safety of Salvianolate injection in the treatment of unstable angina pectoris (UAP). Methods: Using literature databases, we conducted a thorough and systematic retrieval of randomized controlled trials (RCTs) that using Salvianolate injection for treating UAP. The Cochrane Risk of Bias Assessment Tool was used to evaluate the methodological quality of the RCTs, and then the data were extracted and meta-analyzed by RevMan5.2 software. Results: A total of 22 RCTs with 2050 participants were included. The meta-analysis indicated that the combined use of Salvianolate injection and western medicine (WM) in the treatment of UAP can achieve a superior effect in angina pectoris total effective rate (risk ratio [RR] = 1.22, 95% confidence interval [CI] (1.17, 1.27), Z = 10.15, P < 0.00001], and the total effectiveness rate of electrocardiogram [RR = 1.26, 95% CI (1.19,1.34), Z = 7.77, P < 0.00001]. In addition, Salvianolate injection can improve the nitroglycerin withdrawal rate and the serum level of NO, decrease high-sensitivity C-reactive protein. Adverse drug reactions (ADRs) or adverse drug events (ADEs) were reported in 6 RCTs involving 15 cases; however, there were no serious ADRs/ADEs. Conclusion: Based on the systematic review, the combined use of Salvianolate injection and WM in the treatment of UAP can achieve a better effect; however, there was no definitive conclusion about its safety. More the large-sample and multicenter RCTs are needed to support its clinical usage. PMID:28002341

Vibration anesthesia for the reduction of pain with facial dermal filler injections.

PubMed

Mally, Pooja; Czyz, Craig N; Chan, Norman J; Wulc, Allan E

2014-04-01

Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections. The analgesic effect of this method was tested in this study during facial dermal filler injections. The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections. This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds, tear troughs, cheeks, and other facial sites. The injections were administered in a randomly assigned split-face design. One side of the patient's face received vibration together with dermal filler injections, whereas the other side received dermal filler injections alone. The patients completed a posttreatment questionnaire pertaining to injection pain, adverse effects, and preference for vibration with future dermal filler injections. The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections. No adverse events were reported. The majority of the patients (95 %) reported a preference for vibration anesthesia with subsequent dermal filler injections. Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.

PubMed

Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2015-03-01

Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended. © The Author(s) 2014.

Efficacy and safety of closing postcatheterisation pseudoaneurysms with ultrasound-guided thrombin injections using two approaches: bolus versus slow injection. A prospective randomised trial.

PubMed

Lewandowski, Paweł; Maciejewski, Paweł; Wąsek, Wojciech; Pasierski, Tomasz; Budaj, Andrzej

2011-01-01

Thrombin injection is a widely accepted treatment of an iatrogenic arterial pseudoaneurysm. However, the optimal mode of injection and type of pseudoaneurysm amenable to this therapy have yet been established. To compare efficacy and safety of two approaches to ultrasound-guided thrombin injections into a femoral artery pseudoaneurysm with or without long neck that developed as an iatrogenic complication of cardiac catheterisation. Patients were randomised to thrombin administration in a bolus or slow injection. The length and width of aneurysm neck and blood flow velocity in the neck were measured with color Doppler ultrasonography before the closure procedure. Thrombin dose, time to thrombotic occlusion, blood oxygen saturation in a toe of the extremity with the pseudoaneurysm (a marker of silent microembolisation), and clinical signs of distal embolisation were recorded. Between 2006 and 2009, 73 consecutive patients (33 males; mean age 67.8 ± 11.9 years) with femoral pseudoaneurysms complicating cardiac catheterisation were randomised into two groups that were treated with thrombin bolus (n = 40) or slow injection (n = 33). The efficacy of aneurysm closure with either method was similarly high (100% vs 96.8%, NS, respectively) and did not depend on the length and width of the aneurysm neck. Independent risk factors for distal embolisation were: thrombin dose (OR 4.2; 95% CI 0.92-19.3), the length of aneurysm neck (OR 4.66; 95% CI 1.1-19.9), age above 80 years (OR 10.9; 95% CI 1.0-116.8), and bolus treatment (OR 7.6; 95% CI 1.3-44.9). We observed silent microembolisation phenomenon that was common (occurring in 38% of patients in the bolus group vs 33% of patients in the slow injection group) but in most cases asymptomatic. Femoral pseudoaneurysm closure with a low dose of thrombin is a valid and beneficial treatment. Either method (bolus or slow injection) was similarly efficacious and safe even in the subgroup of patients with neckless aneurysms. We observed and confirmed silent microembolisation phenomenon during thrombin injections.

Administering Multiple Injectable Vaccines During a Single Visit—Summary of Findings From the Accelerated Introduction of Inactivated Polio Vaccine Globally

PubMed Central

Patel, Manish; Hampton, Lee M.; Burnett, Eleanor; Ehlman, Daniel C.; Garon, Julie; Cloessner, Emily; Chmielewski, Elizabeth; Hyde, Terri B.; Mantel, Carsten; Wallace, Aaron S.

2017-01-01

Abstract Background. In 2013, the World Health Organization’s (WHO’s) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, “multiple injections”) during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Methods. Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children’s Fund data from 2013–2015 were used to assess multiple-injection visits included in national immunization schedules. Results. Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was largely from developed countries. Parental acceptance of multiple injections was associated with a positive provider recommendation to the caregiver. Findings of the systematic review identified that the intramuscular route is preferred over the subcutaneous route for vaccine administration and that the vastus lateralis muscle is preferred over the deltoid muscle for intramuscular injections. Recommendations on vaccine spacing and procedural preparedness were based on practical necessities, but comparative evidence was not identified. During 2013–2015, 85 countries added IPV to their immunization schedules, 46 (55%) of which adopted a schedule resulting in 3 injectable vaccines being administered in a single visit. Conclusion. The multiple-injection experience identified gaps in guidance for future vaccine introductions. Global partner organizations quickly mobilized to assess, document, and communicate the existing global experience on multiple-injection visits. This evidence-based approach provided reassurance to opinion leaders, health workers, and professional societies, thus encouraging uptake of IPV as a second or third injection in an accelerated manner globally. PMID:28838188

Direct measurements of safety factor profiles with motional Stark effect for KSTAR tokamak discharges with internal transport barriers

NASA Astrophysics Data System (ADS)

Ko, J.; Chung, J.

2017-06-01

The safety factor profile evolutions have been measured from the plasma discharges with the external current drive mechanism such as the multi-ion-source neutral beam injection for the Korea Superconducting Tokamak Advanced Research (KSTAR) for the first time. This measurement has been possible by the newly installed motional Stark effect (MSE) diagnostic system that utilizes the polarized Balmer-alpha emission from the energetic neutral deuterium atoms induced by the Stark effect under the Lorentz electric field. The 25-channel KSTAR MSE diagnostic is based on the conventional photoelastic modulator approach with the spatial and temporal resolutions less than 2 cm (for the most of the channels except 2 to 3 channels inside the magnetic axis) and about 10 ms, respectively. The strong Faraday rotation imposed on the optical elements in the diagnostic system is calibrated out from a separate and well-designed polarization measurement procedure using an in-vessel reference polarizer during the toroidal-field ramp-up phase before the plasma experiment starts. The combination of the non-inductive current drive during the ramp-up and shape control enables the formation of the internal transport barrier where the pitch angle profiles indicate flat or slightly hollow profiles in the safety factor.

New PANDA Tests to Investigate Effects of Light Gases on Passive Safety Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paladino, D.; Auban, O.; Candreia, P.

The large- scale thermal-hydraulic PANDA facility (located at PSI in Switzerland), has been used over the last few years for investigating different passive decay- heat removal systems and containment phenomena for the next generation of light water reactors (Simplified Boiling Water Reactor: SBWR; European Simplified Boiling Water Reactor: ESBWR; Siedewasserreaktor: SWR-1000). Currently, as part of the European Commission 5. EURATOM Framework Programme project 'Testing and Enhanced Modelling of Passive Evolutionary Systems Technology for Containment Cooling' (TEMPEST), a new series of tests is being planned in the PANDA facility to experimentally investigate the distribution of non-condensable gases inside the containment andmore » their effect on the performance of the 'Passive Containment Cooling System' (PCCS). Hydrogen release caused by the metal-water reaction in the case of a postulated severe accident will be simulated in PANDA by injecting helium into the reactor pressure vessel. In order to provide suitable data for Computational Fluid Dynamic (CFD) code assessment and improvement, the instrumentation in PANDA has been upgraded for the new tests. In the present paper, a detailed discussion is given of the new PANDA tests to be performed to investigate the effects of light gas on passive safety systems. The tests are scheduled for the first half of the year 2002. (authors)« less

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

PubMed Central

Gold, Ronald; Barreto, Luis; Ferro, Santiago; Thippawong, John; Guasparini, Roland; Meekison, William; Russell, Margaret; Mills, Elaine; Harrison, Dana; Lavigne, Pierre

2007-01-01

OBJECTIVE The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 μg/mL or greater and 1.0 μg/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine. PMID:18923741

Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

PubMed Central

Fea, Antonio M; Belda, Jose I; Rękas, Marek; Jünemann, Anselm; Chang, Lydia; Pablo, Luis; Voskanyan, Lilit; Katz, L Jay

2014-01-01

Purpose The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol. Patients and methods Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy. Results At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02) at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent inject and medical therapy groups, respectively. A high safety profile was also noted in this study in both the iStent inject and medical therapy groups, as measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse events. Conclusion These data show that the use of iStent inject is at least as effective as two medications, with the clinical benefit of reducing medication burden and assuring continuous treatment with full compliance to implant therapy as well as having a highly favorable safety profile. PMID:24855336

Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis.

PubMed

Fukawa, Taisuke; Yamaguchi, Satoshi; Akatsu, Yorikazu; Yamamoto, Yohei; Akagi, Ryuichiro; Sasho, Takahisa

2017-06-01

An intra-articular injection of platelet-rich plasma (PRP) may be an effective treatment for osteoarthritis (OA). However, its efficacy in ankle OA has not been investigated yet. The purpose of this study was to assess the safety and efficacy of an intra-articular injection of PRP in patients with ankle OA during a 24-week period. Twenty ankles of 20 patients with varus-type ankle OA who received intra-articular injections of PRP were evaluated. PRP was extracted from whole blood by using the double-spin technique. Three injections of 2-mL PRP were administered to the ankle at an interval of 2 weeks under ultrasonographic guidance. Adverse events and efficacy were assessed at 4, 12, and 24 weeks after the last injection. Clinical outcomes were assessed by using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). No serious adverse effects were observed during the follow-up period. The VAS and JSSF scale scores significantly decreased from baseline to 4, 12, and 24 weeks after treatment ( P < .001). The mean score in the pain-related subscale of the SAFE-Q significantly improved from baseline to 12 weeks after treatment ( P = .04). Overall, the amount of pain reduction was maximal at 12 weeks after the last injection, and the effect was reduced at 24 weeks. The patients with late-stage OA had worse scores in all outcomes than those with early-stage OA. Intra-articular injections of PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle OA. PRP treatment can be safe and effective and may be an option in the treatment of ankle OA. Level IV, case series.

Safety of radiofrequency treatment over human skin previously injected with medium-term injectable soft-tissue augmentation materials: a controlled pilot trial.

PubMed

Alam, Murad; Levy, Ross; Pajvani, Urvi; Pavjani, Urvi; Ramierez, James A; Guitart, Joan; Veen, Heather; Gladstone, Hayes B

2006-03-01

Several soft-tissue augmentation materials are now available for reduction of nasolabial fold creases and perioral rhytides. Nasolabial folds and perioral rhytides can also be improved by skin tightening delivered by non-ablative radiofrequency (RF) treatment. The purpose of this study was to assess the safety of RF treatment over skin areas recently injected with medium-term injectable soft-tissue augmentation materials. Five subjects were assigned to the experimental arm (augmentation materials plus RF) and one to the control arm (augmentation materials alone). Each subject received injections of 0.3 mL of hyaluronic acid derivative (Restylane) and calcium hydroxylapatite (Radiesse) 3 cm apart on the upper inner arm. Two weeks later, two non-overlapping passes of RF (Thermage ThermaCool TC) were delivered at 63.5 setting with medium-fast 1.5 cm2 tip over injected sites in all of the experimental subjects. Punch skin biopsies were obtained 3 days later from each of the two injection sites on each subject. Light microscopy and digital photomicrographs obtained at low, medium, and high power showed no difference between filler materials in experimental and control subjects. In both cases filler was evident at the deep dermal-subcutaneous junction. Nodule formation, foreign body extravasation, or hemorrhage/clot was not observed grossly or histologically. Subjects and physicians did not report any difference in signs and symptoms between the experimental and control arms. Slightly increased transitory pain was noted when RF was delivered over filler versus over normal skin. Applying RF treatment over the same area 2 weeks after deep dermal injection with hyaluronic acid derivatives or calcium hydroxylapatite does not appear to cause gross morphological changes in the filler material or surrounding skin. Further studies with different parameters are necessary to confirm these findings. 2006 Wiley-Liss, Inc.

Botulinum Neurotoxin Type-A for the Treatment of Atypical Odontalgia.

PubMed

Cuadrado, María-Luz; García-Moreno, Héctor; Arias, José-Antonio; Pareja, Juan A

2016-09-01

Atypical odontalgia (AO), a subform of persistent idiopathic facial pain, is defined as a continuous toothache in which a thorough examination reveals no dental pathology. AO is believed to be a neuropathic condition, given that some cases are preceded by dental procedures. Different topical and systemic medications have been used for the treatment of AO, but their effect is often unsatisfactory. The authors aimed to assess the effect and safety of botulinum neurotoxin type-A (BoNTA) in a series of patients with AO. Four patients with refractory AO (2 males and 2 females, aged 31-72) were treated with local injections of BoNTA to the painful area. BoNTA was injected at various sites into the gums, and two patients had additional injections in the hard palate or the upper lip. The total dose of BoNTA for each procedure was 15-30 U, and the total number of injection points was 6-12. The follow-up ranged from 6 to 20 months. Two patients received two cycles of BoNTA, while the remaining patients received three and five cycles each, respectively. All patients obtained significant relief with complete or almost complete reduction of pain. The analgesic effect was apparent after a latency period of 3-14 days, and the effect persisted for 2-6 months. There were no adverse events reported from any of the interventions. The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Assessment of the 3He pressure inside the CABRI transient rods - Development of a surrogate model based on measurements and complementary CFD calculations

NASA Astrophysics Data System (ADS)

Clamens, Olivier; Lecerf, Johann; Hudelot, Jean-Pascal; Duc, Bertrand; Cadiou, Thierry; Blaise, Patrick; Biard, Bruno

2018-01-01

CABRI is an experimental pulse reactor, funded by the French Nuclear Safety and Radioprotection Institute (IRSN) and operated by CEA at the Cadarache research center. It is designed to study fuel behavior under RIA conditions. In order to produce the power transients, reactivity is injected by depressurization of a neutron absorber (3He) situated in transient rods inside the reactor core. The shapes of power transients depend on the total amount of reactivity injected and on the injection speed. The injected reactivity can be calculated by conversion of the 3He gas density into units of reactivity. So, it is of upmost importance to properly master gas density evolution in transient rods during a power transient. The 3He depressurization was studied by CFD calculations and completed with measurements using pressure transducers. The CFD calculations show that the density evolution is slower than the pressure drop. Surrogate models were built based on CFD calculations and validated against preliminary tests in the CABRI transient system. Studies also show that it is harder to predict the depressurization during the power transients because of neutron/3He capture reactions that induce a gas heating. This phenomenon can be studied by a multiphysics approach based on reaction rate calculation thanks to Monte Carlo code and study the resulting heating effect with the validated CFD simulation.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

PubMed

Sarduy, M R; García, I; Coca, M A; Perera, A; Torres, L A; Valenzuela, C M; Baladrón, I; Solares, M; Reyes, V; Hernández, I; Perera, Y; Martínez, Y M; Molina, L; González, Y M; Ancízar, J A; Prats, A; González, L; Casacó, C A; Acevedo, B E; López-Saura, P A; Alonso, D F; Gómez, R; Perea-Rodríguez, S E

2015-05-12

We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

[Accelerated desensitization for hymenoptera venom allergy in 30 hours: efficacy and safety in 150 cases].

PubMed

van der Brempt, X; Ledent, C; Mairesse, M

1997-06-01

In this study, we performed 150 desensitizations in 139 Hymenoptera venom allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic patients and 11 patients sensitized to both insects, who received a dual desensitization). We used a rush protocol, allowing injection of a total cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom in 30 hours. Patients were hospitalized, with all emergency precautions for treating systemic reactions. The protocol was well tolerated in 147/150 cases; 3 patients had a benign systemic reaction. Patients received monthly maintenance doses of 100 micrograms venom. 39 patients experienced a field sting during immunotherapy; 2 of them (5%) had a benign systemic reaction. Thus, our rush desensitization protocol seems to be safe and effective.

Post-marketing safety monitoring of shenqifuzheng injection: a solution made of dangshen (Radix Codonopsis) and huangqi (Radix Astragali Mongolici).

PubMed

Ai, Qinghua; Zhang, Wen; Xie, Yanming; Huang, Wenhua; Liang, Hong; Cao, Hui

2014-08-01

To identify the potential risk factors associated with Shenqifuzheng injection (SFI), a solution made of Dangshen (Radix Codonopsis) and Huangqi (Radix Astragali Mongolici), for the timely provision of information to regulatory authorities. A comprehensive analysis of the production process, quality standards, pharmacology, post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions (ADR), case analyses, and systematic reviews, intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital information system (HIS). Sub-acute toxicity tests suggesting that a dose of 15 mL/kg (concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85 per thousand. From March to November 2013, of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI at a dosage and a treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash, chills, feeling cold, palpitation, dyspnea, edema of a lower extremity, palpebral edema, and superficial vein inflammation, among others. This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors. It supports the safety of SFI for clinical, research,and production uses based on objective, reliable, and scientific information to provide safe medication.

Quantification of CO2-FLUID-ROCK Reactions Using Reactive and Non-Reactive Tracers

NASA Astrophysics Data System (ADS)

Matter, J.; Stute, M.; Hall, J. L.; Mesfin, K. G.; Gislason, S. R.; Oelkers, E. H.; Sigfússon, B.; Gunnarsson, I.; Aradottir, E. S.; Alfredsson, H. A.; Gunnlaugsson, E.; Broecker, W. S.

2013-12-01

Carbon dioxide mineralization via fluid-rock reactions provides the most effective and long-term storage option for geologic carbon storage. Injection of CO2 in geologic formations induces CO2 -fluid-rock reactions that may enhance or decrease the storage permanence and thus the long-term safety of geologic carbon storage. Hence, quantitative characterization of critical CO2 -fluid-rock interactions is essential to assess the storage efficiency and safety of geologic carbon storage. In an attempt to quantify in-situ fluid-rock reactions and CO2 transport relevant for geologic carbon storage, we are testing reactive (14C, 13C) and non-reactive (sodium fluorescein, amidorhodamine G, SF5CF3, and SF6) tracers in an ongoing CO2 injection in a basaltic storage reservoir at the CARBFIX pilot injection site in Iceland. At the injection site, CO2 is dissolved in groundwater and injected into a permeable basalt formation located 500-800 m below the surface [1]. The injected CO2 is labeled with 14C by dynamically adding calibrated amounts of H14CO3-solution into the injection stream in addition to the non-reactive tracers. Chemical and isotopic analyses of fluid samples collected in a monitoring well, reveal fast fluid-rock reactions. Maximum SF6 concentration in the monitoring well indicates the bulk arrival of the injected CO2 solution but dissolved inorganic carbon (DIC) concentration and pH values close to background, and a potentially lower 14C to SF6 ratio than the injection ratio suggest that most of the injected CO2 has reacted with the basaltic rocks. This is supported by δ13CDIC, which shows a drop from values close to the δ 13C of the injected CO2 gas (-3‰ VPDB) during breakthrough of the CO2 plume to subsequent more depleted values (-11.25‰ VPDB), indicating precipitation of carbonate minerals. Preliminary mass balance calculations using mixing relationships between the background water in the storage formation and the injected solution, suggest that approximately 85% of the injected CO2 must have reacted along the flow path from the injection well to the monitoring well within less than one year. Monitoring is still going on and we will extend the time series and the mass balance accordingly. Our study demonstrates that by combining reactive and non-reactive tracers, we are able to quantify CO2-fluid-rock interactions on a reservoir scale. [1] Gislason et al. (2010), Int. J. Greenh. Gas Con. 4, 537-545.

Propellant actuated nuclear reactor steam depressurization valve

DOEpatents

Ehrke, Alan C.; Knepp, John B.; Skoda, George I.

1992-01-01

A nuclear fission reactor combined with a propellant actuated depressurization and/or water injection valve is disclosed. The depressurization valve releases pressure from a water cooled, steam producing nuclear reactor when required to insure the safety of the reactor. Depressurization of the reactor pressure vessel enables gravity feeding of supplementary coolant water through the water injection valve to the reactor pressure vessel to prevent damage to the fuel core.

Chemometric Deconvolution of Continuous Electrokinetic Injection Micellar Electrokinetic Chromatography Data for the Quantitation of Trinitrotoluene in Mixtures of Other Nitroaromatic Compounds

DTIC Science & Technology

2014-02-24

Suite 600 Washington, DC 20036 NRL/MR/ 6110 --14-9521 Approved for public release; distribution is unlimited. 1Science & Engineering Apprenticeship...Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/ 6110 --14-9521 Chemometric Deconvolution of Continuous Electrokinetic Injection Micellar... Engineering Apprenticeship Program American Society for Engineering Education Washington, DC Kevin Johnson Navy Technology Center for Safety and

Effect of Vaccine Administration Modality on Immunogenicity and Efficacy

PubMed Central

Zhang, Lu; Wang, Wei; Wang, Shixia

2016-01-01

Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239

Local treatment of the inner ear: a study of three different polymers aimed for middle ear administration.

PubMed

Engmér Berglin, Cecilia; Videhult Pierre, Pernilla; Ekborn, Andreas; Bramer, Tobias; Edsman, Katarina; Hultcrantz, Malou; Laurell, Göran

2015-01-01

A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

Considerations for management of patients with diabetic macular edema: Optimizing treatment outcomes and minimizing safety concerns through interdisciplinary collaboration.

PubMed

Strain, W David; Cos, Xavier; Prünte, Christian

2017-04-01

Diabetes is a growing worldwide epidemic and a leading cause of blindness in working-age people around the world. Diabetic retinopathy (DR) and diabetic macular edema (DME) are common causes of visual impairment in people with diabetes and often indicate the presence of diabetes-associated preclinical micro- and macrovascular complications. As such, patients with DR and DME often display complex, highly comorbid profiles. Several treatments are currently available for the treatment of DME, including anti-vascular endothelial growth factor (VEGF) agents, which are administered via intravitreal injection. While the safety profiles of approved ocular anti-VEGF therapies have been reassuring, the high-risk nature of the DME patient population means that treatment must be carefully considered and a holistic approach to disease management should be taken. This requires multidisciplinary, collaborative care involving all relevant specialties to ensure that patients not only receive prompt treatment for DME but also appropriate consideration is taken of any systemic comorbidities to evaluate and minimize potentially serious safety issues. Copyright © 2017. Published by Elsevier B.V.

Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural) in traditional Chinese medicine injections.

PubMed

Zang, Qingce; Gao, Yang; Huang, Luojiao; He, Jiuming; Lin, Sheng; Jin, Hongtao; Zhang, Ruiping; Abliz, Zeper

2018-03-01

With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150 mm × 2.1 mm, 5 µm) by gradient elution, using methanol-water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/mL and linear over the range of 0.3-30 ng/mL ( r =0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0-109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.

The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.

PubMed

Narita, Takuya; Shintani, Yasunori; Ikebe, Chiho; Kaneko, Masahiro; Harada, Narumi; Tshuma, Nomathamsanqa; Takahashi, Kunihiko; Campbell, Niall G; Coppen, Steven R; Yashiro, Kenta; Sawa, Yoshiki; Suzuki, Ken

2013-09-20

Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data from the Phase 3 REFINE Trials.

PubMed

Dayan, Steven H; Schlessinger, Joel; Beer, Kenneth; Donofrio, Lisa M; Jones, Derek H; Humphrey, Shannon; Carruthers, Jean; Lizzul, Paul F; Gross, Todd M; Beddingfield, Frederick C; Somogyi, Christine

2018-02-01

ATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin. To evaluate the efficacy and safety of ATX-101 by treatment session. This post-hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile. In both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101-treated subjects achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or subject assessment. Furthermore, 19.1% of ATX-101-treated subjects (vs 3.9% of placebo-treated subjects) received fewer than 6 treatment sessions owing to subject satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions. Although up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101-treated subjects achieved an improvement in SMF within 2 to 4 treatment sessions. © 2018 The American Society for Aesthetic Plastic Surgery, Inc.

Coupled Hydro-Mechanical Modeling of Fluid Geological Storage

NASA Astrophysics Data System (ADS)

Castelletto, N.; Garipov, T.; Tchelepi, H. A.

2013-12-01

The accurate modeling of the complex coupled physical processes occurring during the injection and the post-injection period is a key factor for assessing the safety and the feasibility of anthropogenic carbon dioxide (CO2) sequestration in subsurface formations. In recent years, it has become widely accepted the importance of the coupling between fluid flow and geomechanical response in constraining the sustainable pressure buildup caused by fluid injection relative to the caprock sealing capacity, induced seismicity effects and ground surface stability [e.g., Rutqvist, 2012; Castelletto et al., 2013]. Here, we present a modeling approach based on a suitable combination of Finite Volumes (FVs) and Finite Elements (FEs) to solve the coupled system of partial differential equations governing the multiphase flow in a deformable porous medium. Specifically, a FV method is used for the flow problem while the FE method is adopted to address the poro-elasto-plasticity equations. The aim of the present work is to compare the performance and the robustness of unconditionally stable sequential-implicit schemes [Kim et al., 2011] and the fully-implicit method in solving the algebraic systems arising from the discretization of the governing equations, for both normally conditioned and severely ill-conditioned problems. The two approaches are tested against well-known analytical solutions and experimented with in a realistic application of CO2 injection in a synthetic aquifer. References: - Castelletto N., G. Gambolati, and P. Teatini (2013), Geological CO2 sequestration in multi-compartment reservoirs: Geomechanical challenges, J. Geophys. Res. Solid Earth, 118, 2417-2428, doi:10.1002/jgrb.50180. - Kim J., H. A. Tchelepi, and R. Juanes (2011), Stability, accuracy and efficiency of sequential methods for coupled flow and geomechanics, SPE J., 16(2), 249-262. - Rutqvist J. (2012), The geomechanics of CO2 storage in deep sedimentary formations, Geotech. Geol. Eng., 30, 525-551.

The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers.

PubMed

Li, Fang; Weng, Yan; Wang, Lihui; He, Haibing; Yang, Jingyu; Tang, Xing

2010-06-30

Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides. 2010 Elsevier B.V. All rights reserved.

Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility

PubMed Central

Wang, Chung-Cheng; Lee, Cheng-Ling; Kuo, Hann-Chorng

2016-01-01

We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients (p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC. PMID:26999209

A comparison of the oral application and injection routes using the onderstepoort biological products fowl typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens.

PubMed

Purchase, C; Picard, J; McDonald, R; Bisschop, S P R

2008-03-01

This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft) vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks postvaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA) test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %,by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05) in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials.

PubMed

Ahrén, Bo; Carr, Molly C; Murphy, Karen; Perkins, Christopher; Rendell, Marc; Mallory, Jason; Wilson, Timothy; Johnson, Susan

2017-04-01

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM. Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione). Studies of 32months (HARMONY 7), 1year (HARMONY 6), and 3years (HARMONY 1-5), reported similar rates of adverse events (AEs) (84.8%, 82.3%), and serious AEs (13.1%, 12.9%) between albiglutide and all comparators, respectively. AEs that did not differ between the groups included symptomatic or severe hypoglycaemia as well as nausea (12.0%, 11.3%) and vomiting (5.3%, 4.7%) for albiglutide and all comparators, respectively. According to the Medical Dictionary for Regulatory Activities preferred terms, only diarrhoea (13.7%, 9.9%), injection-site reaction (9.0%, 2.0%), and peripheral oedema (4.5%, 6.8%) had at least 2% difference between the albiglutide and all-comparator groups. In a similar integrated analysis, pancreatitis occurred more often with albiglutide (0.3%, 0.1%). Renal and cardiac function did not differ between the two groups. In an integrated analysis of seven phase 3 clinical trials, albiglutide-treated patients experienced frequencies of AEs (including cardiovascular and renal) similar to the all-comparators group treated with other T2DM medications or placebo. Albiglutide treatment was associated with higher rates of diarrhoea and injection-site reactions, but not increased nausea and vomiting, versus all comparators. Copyright © 2017 Elsevier B.V. All rights reserved.

Splenic gene delivery system using self-assembling nano-complex with phosphatidylserine analog.

PubMed

Kurosaki, Tomoaki; Nakasone, Chihiro; Kodama, Yukinobu; Egashira, Kanoko; Harasawa, Hitomi; Muro, Takahiro; Nakagawa, Hiroo; Kitahara, Takashi; Higuchi, Norihide; Nakamura, Tadahiro; Sasaki, Hitoshi

2015-01-01

The recognition of phosphatidylserine on the erythrocyte membrane mediates erythrophagocytosis by resident spleen macrophages. The application of phosphatidylserine to a gene vector may be a novel approach for splenic drug delivery. Therefore, we chose 1,2-dioleoyl-sn-glycero-3-phospho-L-serin (DOPS) as an analogue of phosphatidylserine for splenic gene delivery of plasmid DNA (pDNA). In the present study, we successfully prepared a stable pDNA ternary complex using DOPS and polyethyleneimine (PEI) and evaluated its efficacy and safety. The pDNA/PEI complex had a positive charge and showed high transgene efficacy, although it caused cytotoxicity and agglutination. The addition of DOPS changed the ζ-potential of the pDNA/PEI complex to negative. It is known that anionic complexes are not taken up well by cells. Surprisingly, however, the pDNA/PEI/DOPS complex showed relatively high transgene efficacy in vitro. Fluorescence microscope observation revealed that the pDNA/PEI/DOPS complex internalized the cells while maintaining the complex formation. The injection of the pDNA/PEI complex killed most mice within 24 h at high doses, although all mice in the pDNA/PEI/DOPS complex group survived. The ternary complex with DOPS showed markedly better safety compared with the pDNA/PEI complex. The pDNA/PEI/DOPS complex showed high gene expression selectively in the spleen after intravenous injection into mice. Thus the ternary complex with DOPS can be used to deliver pDNA to the spleen, in which immune cells are abundant. It appears to have an excellent safety level, although further study to determine the mechanism of action is necessary.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

PubMed

Schubert, R; Eickmeier, O; Garn, H; Baer, P C; Mueller, T; Schulze, J; Rose, M A; Rosewich, M; Renz, H; Zielen, S

2009-01-01

Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients. (c) 2008 S. Karger AG, Basel.

Characterization of a high-pressure diesel fuel injection system as a control technology option to improve engine performance and reduce exhaust emissions

NASA Technical Reports Server (NTRS)

Mcfadden, J. J.; Dezelick, R. A.; Barrows, R. R.

1983-01-01

Test results from a high pressure electronically controlled fuel injection system are compared with a commercial mechanical injection system on a single cylinder, diesel test engine using an inlet boost pressure of 2.6:1. The electronic fuel injection system achieved high pressure by means of a fluid intensifier with peak injection pressures of 47 to 69 MPa. Reduced exhaust emissions were demonstrated with an increasing rate of injection followed by a fast cutoff of injection. The reduction in emissions is more responsive to the rate of injection and injection timing than to high peak injection pressure.

A systematic review of dermal fillers for age-related lines and wrinkles.

PubMed

Sturm, Lana P; Cooter, Rodney D; Mutimer, Keith L; Graham, John C; Maddern, Guy J

2011-01-01

Dermal fillers are gaining popularity for rapid aesthetic improvement. Long-term efficacy and safety have not been well documented. The aim of this systematic review was to assess the safety and efficacy of injectable dermal fillers compared with other facial augmentation techniques for the management of age-related lines and wrinkles. Studies including patients receiving injectable semi-permanent or permanent dermal fillers for age-related lines and wrinkles were included in this review. Efficacy outcomes (including changes in skin thickness and patient satisfaction) and safety outcomes (including mortality, lumps and infections) were examined. Three randomized control trials and six case series were included. Permanent and semi-permanent dermal fillers improved subjective ratings of appearance and resulted in higher patient satisfaction than temporary fillers. Long-term efficacy appeared good in the few studies that reported it. Short-term safety appeared favourable. Lumps were reported in all but one study but received little follow-up. Long-term safety data were limited. The treatment of age-related lines and wrinkles with permanent and semi-permanent dermal fillers is more efficacious compared with temporary fillers in those studies that compared them. Case series evidence suggests that these fillers achieve their objective, which is to decrease the visible effects of age-related changes. These fillers appear at least as safe as temporary fillers in the short term in those studies that compared them. Long-term safety could not be determined. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

PubMed

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H F; Karla, Pradeep K; Boddu, Sai H S

2018-02-27

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

PubMed Central

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

Long-Term Suppression of Ocular Neovascularization by Intraocular Injection of Biodegradable Polymeric Particles Containing a Serpin-Derived Peptide

PubMed Central

Shmueli, Ron B.; Ohnaka, Masayuki; Miki, Akiko; Pandey, Niranjan B.; Silva, Raquel Lima e; Koskimaki, Jacob E.; Kim, Jayoung; Popel, Aleksander S.; Campochiaro, Peter A.; Green, Jordan J.

2013-01-01

Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD. PMID:23849876

Reactive Tracer Techniques to Quantitatively Monitor Carbon Dioxide Storage in Geologic Formations

NASA Astrophysics Data System (ADS)

Matter, J. M.; Carson, C.; Stute, M.; Broecker, W. S.

2012-12-01

Injection of CO2 into geologic storage reservoirs induces fluid-rock reactions that may lead to the mineralization of the injected CO2. The long-term safety of geologic CO2 storage is, therefore, determined by in situ CO2-fluid-rock reactions. Currently existing monitoring and verification techniques for CO2 storage are insufficient to characterize the solubility and reactivity of the injected CO2, and to establish a mass balance of the stored CO2. Dissolved and chemically transformed CO2 thus avoid detection. We developed and are testing a new reactive tracer technique for quantitative monitoring and detection of dissolved and chemically transformed CO2 in geologic storage reservoirs. The technique involves tagging the injected carbon with radiocarbon (14C). Carbon-14 is a naturally occurring radioisotope produced by cosmic radiation and made artificially by 14N neutron capture. The ambient concentration is very low with a 14C/12C ratio of 10-12. The concentration of 14C in deep geologic formations and fossil fuels is at least two orders of magnitude lower. This makes 14C an ideal quantitative tracer for tagging underground injections of anthropogenic CO2. We are testing the feasibility of this tracer technique at the CarbFix pilot injection site in Iceland, where approximately 2,000 tons of CO2 dissolved in water are currently injected into a deep basalt aquifer. The injected CO2 is tagged with 14C by dynamically adding calibrated amounts of H14CO3 solution to the injection stream. The target concentration is 12 Bq/kg of injected water, which results in a 14C activity that is 5 times enriched compared to the 1850 background. In addition to 14C as a reactive tracer, trifluormethylsulphur pentafluoride (SF5CF3) and sulfurhexafluoride (SF6) are used as conservative tracers to monitor the transport of the injected CO2 in the subsurface. Fluid samples are collected for tracer analysis from the injection and monitoring wells on a regular basis. Results show a fast reaction of the injected CO2 with the ambient reservoir fluid and rocks. Mixing and in situ CO2-water-rock reactions are detected by changes in the different tracer ratios. The feasibility of 14C as a reactive tracer for geologic CO2 storage also depends on the analytical technique used to measure 14C activities. Currently, 14C is analyzed using Accelerator Mass Spectrometery (AMS), which is expensive and requires centralized facilities. To enable real time online monitoring and verification, we are developing an alternative detection method for radiocarbon. The IntraCavity OptoGalvanic Spectroscopy (ICOGS) system is using a CO2 laser to detect carbon isotope ratios at environmental levels. Results from our prototype of this bench-top technology demonstrate that an ICOGS system can be used in a continuous mode with analysis times of the order of minutes, and can deliver data of similar quality as AMS.

Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

PubMed Central

Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo

2012-01-01

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.   Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531

Comparison of two ultrasound-guided injection techniques targeting the sacroiliac joint region in equine cadavers.

PubMed

Stack, John David; Bergamino, Chiara; Sanders, Ruth; Fogarty, Ursula; Puggioni, Antonella; Kearney, Clodagh; David, Florent

2016-09-20

To compare the accuracy and distribution of injectate for cranial (CR) and caudomedial (CM) ultrasound-guided injections of equine sacroiliac joints. Both sacroiliac joints from 10 lumbosacropelvic specimens were injected using cranial parasagittal (CR; curved 18 gauge, 25 cm spinal needles) and caudomedial (CM; straight 18 gauge, 15 cm spinal needles) ultrasound-guided approaches. Injectate consisted of 4 ml iodinated contrast and 2 ml methylene blue. Computed tomographical (CT) scans were performed before and after injections. Time for needle guidance and repositioning attempts were recorded. The CT sequences were analysed for accuracy and distribution of contrast. Intra-articular contrast was detected in sacroiliac joints following 15/40 injections. The CR and CM approaches deposited injectate ≤2 cm from sacroiliac joint margins following 17/20 and 20/20 injections, respectively. Median distance of closest contrast to the sacroiliac joint was 0.4 cm (interquartile range [IQR]: 1.5 cm) for CR approaches and 0.6 cm (IQR: 0.95 cm) for CM approaches. Cranial injections resulted in injectate contacting lumbosacral intertransverse joints 15/20 times. Caudomedial injections were perivascular 16/20 times. Safety and efficacy could not be established. Cranial and CM ultrasound-guided injections targeting sacroiliac joints were very accurate for periarticular injection, but accuracy was poor for intra-articular injection. Injectate was frequently found in contact with interosseous sacroiliac ligaments, as well as neurovascular and synovial structures in close vicinity of sacroiliac joints.

Injection System for Multi-Well Injection Using a Single Pump

PubMed Central

Wovkulich, Karen; Stute, Martin; Protus, Thomas J.; Mailloux, Brian J.; Chillrud, Steven N.

2015-01-01

Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a three-month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over three months; an even distribution of flow to each injection well was maintained (RSD <4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air-stable liquids to multiple injection points with a single pump. PMID:26140014

Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie's disease using a new modified shortened protocol.

PubMed

Abdel Raheem, Amr; Capece, Marco; Kalejaiye, Odunayo; Abdel-Raheem, Tarek; Falcone, Marco; Johnson, Mark; Ralph, Oliver G; Garaffa, Giulio; Christopher, Andrew N; Ralph, David J

2017-11-01

To evaluate the efficacy and safety of collagenase clostridium histolyticum (CCH; Xiapex ® , Xiaflex ® ) in the treatment of Peyronie's disease (PD) using a new modified treatment protocol that aims at reducing the number of injections needed and reducing patient visits, thus reducing the duration and cost of treatment. A prospective study of 53 patients with PD who had treatment with CCH at a single centre using a new modified protocol. The angle of curvature assessment after an intracavernosal injection of prostaglandin E1, the International Index of Erectile Function (IIEF) and Peyronie's Disease Questionnaire (PDQ) were completed at baseline and at week 12 (4 weeks after the last injection). The Global Assessment of Peyronie's disease (GAPD) questionnaire was completed at week 12. Under a penile block of 10 mL plain lignocaine 1%, a total of three intralesional injections of CCH (0.9 mg) were given at 4-weekly intervals using a new modified injection technique. In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis to mechanically stretch the plaque. Investigator modelling was not performed. The mean (range) penile curvature at baseline was 54 (30-90)°. Of the 53 patients in the study, 51 patients (96.2%) had an improvement in the angel of curvature by a mean (range) of 17.36 (0-40)° or 31.4 (0-57)% from baseline after three CCH injections. The final mean (range) curvature was 36.9 (12-75)° (P < 0.001). There was an improvement in each of the IIEF questionnaire domains, all three PDQ domains and the GAPD. CCH was well tolerated by all patients with only mild and transient local adverse events. The new shortened protocol using CCH treatment is safe, effective, and cost efficient. The results of using only three CCH injections according to this modified protocol are comparable to those of the clinical trials that used eight CCH injections. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Efficacy and safety of newly developed cross-linked dextran gel injection for glans penis augmentation with a novel technique

PubMed Central

Yang, Dae Yul; Ko, Kyungtae; Lee, Seong Ho; Moon, Du Geon; Kim, Jong Wook; Lee, Won Ki

2018-01-01

There is no safe and effective standard method for glans penis augmentation. Furthermore, there has been scant research on glans penis augmentation due to a poor understanding of glans anatomy, technical difficulty, and a lack of suitable substances for augmentation. Cross-linked dextran gel is a newly developed filler for soft-tissue augmentation. We evaluated the efficacy and safety of using a novel technique to inject cross-linked dextran gel for glans penis augmentation during a 24-week follow-up study. This prospective, single-arm, multicenter study enrolled twenty healthy adult men who underwent glans penis augmentation between June and August 2013. Cross-linked dextran gel was injected into the glans penis using a simple and easy technique. The sizes of the glans penis and individual satisfaction were assessed. Any adverse event was also reported. A total of 18 individuals were analyzed; two of them were lost to follow-up. The mean procedure time and injected volume were about 30 min and 6.6 ± 0.9 ml, respectively. The mean surface areas of the glans at baseline and 24 weeks were 20.0 ± 3.5 cm2 and 33.6 ± 5.4 cm2, respectively, representing a mean increase of 68.7% ± 14.0% (P < 0.001). Sixteen individuals (88.9%) were satisfied with the outcomes, and none were dissatisfied. There were no serious adverse events during the study. Cross-linked dextran gel injection for glans penis augmentation was easy and showed a significant augmentative effect on the glans penis, good durability, and was well tolerated without serious adverse events. Therefore, cross-linked dextran gel injection may be an effective, new technique for glans penis augmentation. PMID:28303807

Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.

PubMed

Munier, Francis L; Soliman, Sameh; Moulin, Alexandre P; Gaillard, Marie-Claire; Balmer, Aubin; Beck-Popovic, Maja

2012-08-01

The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.

PubMed

Rudinsky, A J; Adin, C A; Borin-Crivellenti, S; Rajala-Schultz, P; Hall, M J; Gilor, C

2015-04-01

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy and safety of 1alpha-hydroxyvitamin D3 for prevention of parturient paresis.

PubMed

Gast, D R; Marquardt, J P; Jorgensen, N A; Deluca, H F

1977-12-01

Four trials involved intravenous or intramuscular injections of 1alpha-hydroxyvitavin D3 to test efficacy in preventing parturient paresis. Use of .1 mg intravenously afforded total protection compared with an incidence of 33% (2/6) in controls. Intramuscular injections of .1 mg in 2 ml propylene glycol and .3, .5, and 1.0 mg in 5 ml corn oil resulted in 0, 15.7, 20, and 0% incidence of parturient paresis compared with 33, 16.7, 37.5, and 37.5% incidence of parturient paresis in the controls. There was a rapid increase in serum calcium (12 to 24 h) in response to intravenous treatment, whereas the response to intramuscular injections was gradual but was maintained longer. To evaluate the safety of 1alpha-hydroxyvitamin D3, eight cows, two per treatment, were given intramuscular doses of .5, 1.0, 1.5, or 3.0 mg (three 1.0 mg injections) in 5 ml corn oil. No clinical or pathological evidence of hypervitaminosis C or soft tissue calcification was found. Tissue taken from the injection site 15 days after last injection contained 3 to 38 IU vitamin D activity per 100 g wet tissue compared with control of 8 to 15 IU per 100 g. Total vitamin D activity of milk taken the 11th milking postpartum from cows receiving .5 or 1.0 mg had a mean of 13.4 and 22.6 IU vitamin D activity per liter compared to 19 IU per liter for control milk. Milk from the 5th milking postpartum in the cows receiving .5 mg had a mean activity of 14.5 IU per liter. Milk from animals slaughtered for retention studies had a mean activity of 22 IU per liter.

Flow Range of Centrifugal Compressor Being Extended

NASA Technical Reports Server (NTRS)

Skoch, Gary J.

2001-01-01

General Aviation will benefit from turbine engines that are both fuel-efficient and reliable. Current engines fall short of their potential to achieve these attributes. The reason is compressor surge, which is a flow stability problem that develops when the compressor is subjected to conditions that are outside of its operating range. Compressor surge can occur when fuel flow to the engine is increased, temporarily back pressuring the compressor and pushing it past its stability limit, or when the compressor is subjected to inlet flow-field distortions that may occur during takeoff and landing. Compressor surge can result in the loss of an aircraft. As a result, engine designers include a margin of safety between the operating line of the engine and the stability limit line of the compressor. Unfortunately, the most efficient operating line for the compressor is usually closer to its stability limit line than it is to the line that provides an adequate margin of safety. A wider stable flow range will permit operation along the most efficient operating line of the compressor, improving the specific fuel consumption of the engine and reducing emissions. The NASA Glenn Research Center is working to extend the stable flow range of the compressor. Significant extension has been achieved in axial compressors by injecting air upstream of the compressor blade rows. Recently, the technique was successfully applied to a 4:1 pressure ratio centrifugal compressor by injecting streams of air into the diffuser. Both steady and controlled unsteady injection were used to inject air through the diffuser shroud surface and extend the range. Future work will evaluate the effect of air injection through the diffuser hub surface and diffuser vanes with the goal of maximizing the range extension while minimizing the amount of injected air that is required.

Efficacy and Safety of Postoperative Pain Relief by Parecoxib Injection after Laparoscopic Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Huang, Jun-Ming; Lv, Zheng-Tao; Zhang, Ya-Nan; Jiang, Wen-Xiu; Li, Han-Ning; Nie, Ming-Bo

2017-10-17

This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged. © 2017 World Institute of Pain.

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

PubMed

Arana, Jorge E; Harrington, Theresa; Cano, Maria; Lewis, Paige; Mba-Jonas, Adamma; Rongxia, Li; Stewart, Brock; Markowitz, Lauri E; Shimabukuro, Tom T

2018-03-20

The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data. Published by Elsevier Ltd.

Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

NASA Astrophysics Data System (ADS)

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Matsuyama, Keigo; Nakazato, Yasutaro; Arimori, Akihiro; Isobe, Masaaki; Tochigi, Saeko; Kondoh, Sayuri; Hirai, Toshiro; Akase, Takanori; Yamashita, Takuya; Yamashita, Kohei; Yoshida, Tokuyuki; Nagano, Kazuya; Abe, Yasuhiro; Yoshioka, Yasuo; Kamada, Haruhiko; Imazawa, Takayoshi; Itoh, Norio; Kondoh, Masuo; Yagi, Kiyohito; Mayumi, Tadanori; Tsunoda, Shin-ichi; Tsutsumi, Yasuo

2012-02-01

We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.

Data driven CAN node reliability assessment for manufacturing system

NASA Astrophysics Data System (ADS)

Zhang, Leiming; Yuan, Yong; Lei, Yong

2017-01-01

The reliability of the Controller Area Network(CAN) is critical to the performance and safety of the system. However, direct bus-off time assessment tools are lacking in practice due to inaccessibility of the node information and the complexity of the node interactions upon errors. In order to measure the mean time to bus-off(MTTB) of all the nodes, a novel data driven node bus-off time assessment method for CAN network is proposed by directly using network error information. First, the corresponding network error event sequence for each node is constructed using multiple-layer network error information. Then, the generalized zero inflated Poisson process(GZIP) model is established for each node based on the error event sequence. Finally, the stochastic model is constructed to predict the MTTB of the node. The accelerated case studies with different error injection rates are conducted on a laboratory network to demonstrate the proposed method, where the network errors are generated by a computer controlled error injection system. Experiment results show that the MTTB of nodes predicted by the proposed method agree well with observations in the case studies. The proposed data driven node time to bus-off assessment method for CAN networks can successfully predict the MTTB of nodes by directly using network error event data.

Efficacy and safety of mepivacaine compared with lidocaine in local anaesthesia in dentistry: a meta-analysis of randomised controlled trials.

PubMed

Su, Naichuan; Liu, Yan; Yang, Xianrui; Shi, Zongdao; Huang, Yi

2014-04-01

The objective of the study was to assess the efficacy and safety of mepivacaine compared with lidocaine used in local anaesthesia in dentistry. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure and WHO International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomised controlled trials comparing mepivacaine with lidocaine in terms of efficacy and safety. Twenty-eight studies were included, of which 15 had low risk of bias and 13 had moderate risk of bias. In comparison with 2% lidocaine with 1:100,000 adrenaline, 3% mepivacaine showed a lower success rate (P = 0.05), a shorter onset time of pulpal anaesthesia (P = 0.0005), inferior pain control during injection phase and superior inhibition of heart rate increase (P < 0.0001). In contrast, 2% mepivacaine with 1:100,000 adrenaline gave a higher success rate (P < 0.00001), a similar onset time of pulpal anaesthesia (P = 0.34) and superior pain control during injection phase (P < 0.0001); 2% mepivacaine with 1:20,000 levonordefrin had the same success rate (P = 0.69) and similar onset time of pulpal anaesthesia (P = 0.90). In addition, 3% mepivacaine had shorter onset time (P = 0.004), same level of success rate (P = 0.28) and similar pain control during injection and postinjection compared with 2% lidocaine with 1:50,000 adrenaline. Given the efficacy and safety of the two solutions, 2% mepivacaine with vasoconstrictors is better than 2% lidocaine with vasoconstrictors in dental treatment. Meanwhile, 3% plain mepivacaine is better for patients with cardiac diseases. © 2014 FDI World Dental Federation.

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

PubMed

Johannsson, Gudmundur; Feldt-Rasmussen, Ulla; Håkonsson, Ida Holme; Biering, Henrik; Rodien, Patrice; Tahara, Shigeyuki; Toogood, Andrew; Rasmussen, Michael Højby

2018-05-01

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin ® . Local tolerability and treatment satisfaction were also assessed. 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( n  = 61) or once-daily Norditropin ( n  = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( P  = 0.0171). In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 The authors.

Evaluation of boldenone as a growth promoter in broilers: safety and meat quality aspects.

PubMed

Elmajdoub, Abdelrazzag; Garbaj, Aboubaker; Abolghait, Said; El-Mahmoudy, Abubakr

2016-04-01

The object of this study was to evaluate the safety and meat quality criteria in broilers following intramuscular injection of boldenone. Twenty-four broiler chicks, divided into two groups, were used in the present study. Boldenone was injected intramuscularly at a single-dose level of 5 mg/kg body weight into 12 broiler chicks at 2 weeks old; the other 12 chicks were injected with sesame oil and kept as controls. Blood samples were collected from the wing and metatarsal veins after 1, 2, and 3 weeks through the experimental course for hematological and clinic-chemical safety parameters. On the last day, chicks were humanely sacrificed and livers and kidneys were removed for histopathological examination. Breast muscles were also removed to assess meat-quality parameters. Boldenone significantly (p < 0.05) increased total erythrocytic count and hemoglobin and hematocrit values, while mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration indices decreased. Leukogram showed leukopenia, lymphopenia, and granulocytosis (p < 0.05) as compared to control. Hepatorenal biomarkers, including alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine were significantly (p < 0.05) higher than the corresponding control values. Additionally, boldenone significantly (p < 0.05) increased metabolic markers, including total protein, globulins, cholesterol, triacylglycerols, and glucose, with parallel decreases in albumin and albumin/globulin ratio. Degenerative changes were recorded in liver and kidney tissues from chicks treated with boldenone. Muscle samples exhibited raised pH values and higher microbial counts as compared to the corresponding control. These data may discourage the use of boldenone as a growth promoter in broilers due to safety and meat quality reasons. Copyright © 2016. Published by Elsevier B.V.

Active SMS-based influenza vaccine safety surveillance in Australian children.

PubMed

Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6-71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

Short-term clinical evaluation of intralesional triamcinolone acetonide injection for ulcerative oral lichen planus.

PubMed

Xia, Juan; Li, Chunyang; Hong, Yun; Yang, Linglan; Huang, Yulei; Cheng, Bin

2006-07-01

Efforts are made in a continued searching for novel therapies for symptomatic oral lichen planus (OLP). This study aimed to evaluate the efficacy and safety of intralesional triamcinolone acetonide (TA) injection for ulcerative OLP. Forty-five patients with clinical and histologically confirmed ulcerative OLP on bilateral buccal mucosa, one for treatment and the other for control, were studied. All participants received 0.5 ml TA (40 mg/ml) on experimental sites. Visual analogue scale score and lesion areas were recorded at the time of injection and 1-week interval. After 2 weeks, if the treated ulceration reduced < 81% in size, a second injection was given. The treated group gave rapid relief of signs and symptoms, while the control group showed minimal decrease. 38 (84.4%) patients demonstrated complete response in ulceration size. No complications were noted with TA injections. Intralesional TA injection in ulcerative OLP is effective and safe in achieving lesion and pain regression.

[Development of injection containers for patient and medical staff].

PubMed

Kawasaki, Yoichi; Sendo, Toshiaki

2015-01-01

Recently, there has been a transition from glass to plastic injection containers in Japan. In our previous study, we suggested that plastic containers had less impurity contamination than glass containers. However, the use of some plasticizers has been limited because of their endocrine disrupting effects. Therefore, contamination has been a concern due to chemicals in injection solution packed with plastic containers. Indeed, in our recent study, photoinitiators were detected in an injection solution coming from plastic containers. Photoinitiators mainly exist in ink. We therefore speculated that ink originating from a photoinitiator directly printing on plastic containers had migrated into the injection solutions. In a clinical setting, plastic containers are very tractable because they are lightweight and less breakable. On the other hand, from a safety view point, these containers may be hazardous because of permeation by steam, ambient air or photoinitiators. In the present symposium, we will discuss the risk of photoinitiators leaking into injection solution packed with plastic containers, and countermeasures to avoid this risk.

Accidental needle sticks, the Occupational Safety and Health Administration, and the fallacy of public policy.

PubMed

Wolf, Bruce L; Marks, Albert; Fahrenholz, John M

2006-07-01

Current Occupational Safety and Health Administration (OSHA) guidelines mandate the use of safety needles when allergy injections are given. Safety needles for intradermal testing remain optional. Whether safety needles reduce the number of accidental needle sticks (ANSs) in the outpatient setting has yet to be proven. To determine the rate of ANSs with new (safety) needles vs old needles used in allergy immunotherapy and intradermal testing. Allergy practices from 22 states were surveyed by e-mail. Seventy practices (28%) responded to the survey. Twice as many ANSs occurred in practices giving immunotherapy when using new needles vs old needles (P < .01). The rate of ANSs was roughly the same for intradermal testing with new needles vs old needles. These findings further question whether OSHA's guidelines for safety needle use in outpatient practice need revision and if allergy practices might be excluded from the requirement to use safety needles.

An investigation of the performance of an electronic in-line pump system for diesel engines

NASA Astrophysics Data System (ADS)

Fan, Li-Yun; Zhu, Yuan-Xian; Long, Wu-Qiang; Ma, Xiu-Zhen; Xue, Ying-Ying

2008-12-01

WIT Electronic Fuel System Co., Ltd. has developed a new fuel injector, the Electronic In-line Pump (EIP) system, designed to meet China’s diesel engine emission and fuel economy regulations. It can be used on marine diesel engines and commercial vehicle engines through different EIP systems. A numerical model of the EIP system was built in the AMESim environment for the purpose of creating a design tool for engine application and system optimization. The model was used to predict key injection characteristics under different operating conditions, such as injection pressure, injection rate, and injection duration. To validate these predictions, experimental tests were conducted under the conditions that were modeled. The results were quite encouraging and in agreement with model predictions. Additional experiments were conducted to study the injection characteristics of the EIP system. These results show that injection pressure and injection quantity are insensitive to injection timing variations, this is due to the design of the constant velocity cam profile. Finally, injection quantity and pressure vs. pulse width at different cam speeds are presented, an important injection characteristic for EIP system calibration.

Single hole multi-parameter downhole monitoring of shallow CO2 injection at Maguelone experimental site (Languedoc, France)

NASA Astrophysics Data System (ADS)

Denchik, N.; Pezard, P. A.; Abdoulghafour, H.; Lofi, J.; Neyens, D.; Perroud, H.; Henry, G.; Rolland, B.

2015-12-01

The Maguelone experimental site for shallow subsurface hydrogeophysical monitoring, located along the Mediterranean Lido near Montpellier (Languedoc, France) has proven over the years to provide a unique setup to test gas storage monitoring methods at shallow depth. The presence of two small reservoirs (R1: 13-16 m and R2: 8-9 m) with impermeable boundaries provides an opportunity to study a saline formation for geological storage both in the field and in a laboratory context. This integrated monitoring concept was first applied at Maguelone for characterization of the reservoir state before and during N2 and CO2 injections as part of the MUSTANG FP7 project. Multimethod monitoring was shown to be sensitive to gas storage within a saline reservoir with clear data changes immediately after the beginning of injection. Pressure remains the first indicator of gas storage at ~8-9 m depth in a small permeable unit (gravels/shells) under the Holocene lagoonal sediments. A good correlation is also obtained between the resistivity response and geochemical parameters from pore fluid sampling (pH, minor and major cation concentrations) at this depth. On the basis of previous gas injection experiments, new holes were drilled as part of PANACEA (EC project) in 2014, including an injection hole targeted for injection at 8-9 m depth in the R2 reservoir in order to have gas injection and gas storage at the same depth, a single hole multi-parameter observatory, and a seismic source hole. A total volume of ~48 m3 of CO2 was injected over ~2 hours on December 4, 2014. The injection rate varied from 24 to 30 m3/h, with a well head pressure of 1.8 bars. All downhole monitoring technologies (resistivity, temperature, pressure, SP and seismic measurements) were combined in the single hole observatory. Such device allows monitoring the downhole system before and after injection and the gas migration from the injection hole, helping to characterize the transport mechanism. Decreasing the number of monitoring-measurements and verification (MMV) holes enables a significant decrease of gas leakage risk. This specific monitoring approach is expected to give information about the safety and reliability of CO2 storage operation that guarantees public acceptance.

Use of platelet rich plasma for the treatment of bicipital tendinopathy in spinal cord injury:: a pilot study.

PubMed

Ibrahim, Victor M; Groah, Suzanne L; Libin, Alexander; Ljungberg, Inger H

2012-01-01

The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) in the nonoperative management of shoulder tendinopathy amongst individuals with spinal cord injury. This objective was met by completing a pilot study on the effectiveness and safety of a PRP injection into the biceps tendon demonstrating clinical and ultrasonagraphic pathology. Recent analysis of the preliminary pilot data has demonstrated remarkably convincing results demonstrating both the safety and efficacy of this novel intervention.

Preclinical Mammalian Safety Studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA).

PubMed

Wagner, Michael J; Mitra, Rahul; McArthur, Mark J; Baze, Wallace; Barnhart, Kirstin; Wu, Sherry Y; Rodriguez-Aguayo, Cristian; Zhang, Xinna; Coleman, Robert L; Lopez-Berestein, Gabriel; Sood, Anil K

2017-06-01

To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice ( N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered >225 μg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

PubMed Central

Hartmann, Kathrin I.; Nieto, Alejandra; Wu, Elizabeth C.; Freeman, William R.; Kim, Jae Suk; Chhablani, Jay; Sailor, Michael J.

2013-01-01

Abstract Purpose To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography–electrospray ionization–multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected. PMID:23448595

Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers

PubMed Central

Flaim, JoAnn D.; Grundy, John S.; Baker, Brenda F.; McGowan, Mary P.; Kastelein, John J. P.

2014-01-01

Background Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low‐density lipoprotein (LDL) cholesterol, non‐high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA‐approved subcutaneous dose of 200 mg once weekly. Methods and Results A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty‐four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post‐dose elevation of C‐reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. Conclusions This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer‐term studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061814. PMID:24627419

Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers.

PubMed

Flaim, Joann D; Grundy, John S; Baker, Brenda F; McGowan, Mary P; Kastelein, John J P

2014-03-13

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA-approved subcutaneous dose of 200 mg once weekly. A short-term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty-four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post-distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post-dose elevation of C-reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer-term studies. http://www.clinicaltrials.gov. Unique identifier: NCT01061814.

Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers.

PubMed

Hopkins, Robert J; Daczkowski, Nancy F; Kaptur, Paulina E; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L; Bernton, Edward

2013-06-26

A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax(®) (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18-50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA+0.5mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA+0.25mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA+0.5mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA+0.25mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909. Copyright © 2013 Elsevier Ltd. All rights reserved.

Can a Compact Pre-Filled Auto-Disable Injection System (cPAD) Save Costs for DTP-HepB-Hib Vaccine as Compared with Single-Dose (SDV) and Multi-Dose Vials (MDV)? Evidence from Cambodia, Ghana, and Peru.

PubMed

Nogier, Cyril; Hanlon, Patrick; Wiedenmayer, Karin; Maire, Nicolas

2015-03-01

A compact pre-filled auto-disable injection (cPAD) presentation is being developed for the fully liquid pentavalent DTP-HepB-Hib vaccine. A cost analysis (CA) to compare this presentation with the presently used single-dose vial (SDV) and multi-dose vial (MDV) was conducted in Cambodia, Ghana, and Peru. The CA included the development of an excel-based costing model and considered the costs of vaccine, safe injection equipment, procurement, storage, transport and distribution, vaccine administration by health staff, medical waste management, start-up activities, as well as coverage, birth cohort, vaccine, and safe injection equipment wastage rates. The outcome was the change in cost per pentavalent fully immunized child (PFIC) for a switch to cPAD. Field visits to health facilities, and interviews with key informants from immunization services and regulatory authorities, were conducted to collect data and to test the costing model in country context. Cost data were also obtained from manufacturers, published price lists, and author estimates. A sensitivity analysis (SA) was conducted to explore possible variations in values of data collected. Based on vaccine price trends estimated for 2016, cPAD is less costly in Ghana [incremental cost per PFIC: $US-0.59 (-6.46 %)] than the current presentation (ten-dose MDV) and in Peru (SDV): $US-0.89 (-7.14 %). In Cambodia, cPAD is more costly than SDV: $US+0.33 (+3.90 %). The most significant cost item per PFIC is the vaccine (reflecting wastage rates) in all presentations. The dominance of the vaccine price per dose and, to a lesser extent, the wastage rates in the incremental cost per PFIC show potential to simplify future analyses. Other relevant considerations at country level for a change of presentation include the potential for improved safety with cPAD, planned introduction of other vaccines, environmental and safety issues, and financial sustainability.

Subcutaneous administration of paclitaxel in dogs with cancer: A preliminary study

PubMed Central

Silva, Daniella M.; Franciosi, Aline I.; Pezzini, Paula C.F.; Guérios, Simone D.

2015-01-01

Intravenous paclitaxel has been underused in dogs due to severe and acute hypersensitivity reactions. Subcutaneous (SC) administration of paclitaxel and its safety are unknown. In this preliminary study, SC administration of paclitaxel was evaluated for hypersensitivity reactions and toxicity in 21 dogs with advanced cancer. Dogs received 1 to 5 paclitaxel doses, ranging from 85 to 170 mg/m2, SC every 14 or 21 days. A total of 40 paclitaxel doses were administered and none of the 21 dogs developed systemic or acute local hypersensitivity reactions. Severe skin lesions at the injection site developed in 2 dogs after the 4th injection at the same location. Grade 4 neutropenia was observed in 50% of the dogs 5 days after the first treatment at 115 mg/m2 (n = 14). Two animals developed Grade 5 diarrhea and died likely due to hemodynamic failure or sepsis. Paclitaxel can be administered SC in dogs with no hypersensitivity reaction. PMID:26246628

Safety Studies for Use of Adipose Tissue‐Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial

PubMed Central

Riester, Scott M.; Denbeigh, Janet M.; Lin, Yang; Jones, Dakota L.; de Mooij, Tristan; Lewallen, Eric A.; Nie, Hai; Paradise, Christopher R.; Radel, Darcie J.; Dudakovic, Amel; Camilleri, Emily T.; Larson, Dirk R.; Qu, Wenchun; Krych, Aaron J.; Frick, Matthew A.; Im, Hee‐Jeong; Dietz, Allan B.; Smith, Jay

2016-01-01

Abstract Adipose‐derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra‐articular joint space. Culture‐expanded human AMSCs grown in human platelet‐lysate were delivered via intra‐articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x‐ray, magnetic resonance imaging, and histopathology. Intra‐articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra‐articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910–922 PMID:28297568

Deflectometric analysis of high volume injection molds for production of occupational eye wear.

PubMed

Speck, Alexis; Zelzer, Benedikt; Speich, Marco; Börret, Rainer; Langenbucher, Achim; Eppig, Timo

2013-12-01

Most of the protective eye wear devices currently on the market are manufactured on simple polycarbonate shields, produced by injection molding techniques. Despite high importance of optical quality, injection molds are rarely inspected for surface quality before or during the manufacturing process. Quality degradation is mainly monitored by optical testing of the molded parts. The purpose of this work was to validate a non-contact deflectometric measurement technique for surface and shape analysis of injection molds to facilitate deterministic surface quality control and to monitor minor conformity of the injection mold with the design data. The system is based on phase-measuring deflectometry with a operating measurement field of 80×80 mm(2) (±18° slope), a lateral resolution of 60μm and a local sensitivity of some nanometers. The calibration was tested with a calibration normal and a reference sphere. The results were crosschecked against a measurement of the same object with a tactile coordinate measuring machine. Eight injection molds for production of safety goggles with radii of +58mm (convex) and -60mm (concave) were measured in this study. The molds were separated into two groups (cavity 1 and 2 of the tool with different polishing techniques) and measured to test whether the measurement tool could extract differences. The analysis was performed on difference height between the measured surface and the spherical model. The device could derive the surface change due to polishing and discriminate between both polishing techniques, on the basis of the measured data. The concave nozzle sides of the first group (cavity 1) showed good shape conformity. In comparison, the nozzle sides of the second group (cavity 2) showed local deviations from design data up to 14.4μm. Local form variations of about 5μm occurred in the field of view. All convex ejector sides of both groups (cavity 1 and 2) showed rotational symmetric errors and the molds were measured in general flatter than design data. We applied a deflectometric system for measuring and evaluating specular reflective injection molding tools to optimize the production process of occupational eye wear. The surface quality could be inline monitored in the production processes for actual spectacle models. Copyright © 2013. Published by Elsevier GmbH.

Injection practices in a metropolis of North India: perceptions, determinants and issues of safety.

PubMed

Kotwal, A; Priya, R; Thakur, R; Gupta, V; Kotwal, J; Seth, T

2004-08-01

At least 50 percent of the injections administered each year are unsafe, more particularly in developing countries, posing serious health risks. An initial assessment to describe injection practices; their determinants and adverse effects can prevent injection-associated transmission of blood borne pathogens by reducing injection frequency and adoption of safe injection practices. To assess the injection practices in a large metropolitan city encompassing varied socio-cultural scenarios. STUDY SETTING AND DESIGN: Field based cross sectional survey covering urban non-slum, slum and peri-urban areas of a large metropolitan city. Injection prescribers, providers and community members selected by random sampling from the study areas. Pre tested questionnaires assessed knowledge and perceptions of study subjects towards injections and their possible complications. Observation of the process of injection and prescription audit also carried out. MS Access for database and SPSS ver 11 for analysis. Point estimates, 95% confidence intervals, Chi Square, t test, one-way ANOVA. The per capita injection rate was 5.1 per year and ratio of therapeutic to immunization injections was 4.4:1. Only 22.5%of injections were administered with a sterile syringe and needle. The level of knowledge about HIV and HBV transmission by unsafe injections was satisfactory amongst prescribers and community, but inadequate amongst providers. HCV was known to a very few in all the groups. The annual incidence of needle stick injuries among providers was quite high. A locally relevant safe injection policy based on multi disciplinary approach is required to reduce number of injections, unsafe injections and their attendant complications.

Safety and effectiveness of a single and repeat intramuscular injection of a GnRH vaccine (GonaCon™) in adult female domestic cats.

PubMed

Vansandt, L M; Kutzler, M A; Fischer, A E; Morris, K N; Swanson, W F

2017-04-01

Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats. A pilot study was undertaken to evaluate the short-term safety of a single GonaCon immunization, assess the consequences of vaccinated cats receiving an accidental second GonaCon injection and determine the humoral immune response to immunization. During Phase 1, cats in Group A (n = 3) received a single intramuscular injection of GonaCon and Group B (n = 3) received a single intramuscular injection of saline. During Phase 2, Group A received a second GonaCon injection and Group B received their initial GonaCon injection. All cats developed GnRH antibodies within 30 days of vaccine administration. The endpoint titre (1:1,024,000) was similar among all cats, and levels remained high throughout the duration of the study. Four cats developed a sterile, painless, self-limiting mass at the site of injection. The mean number of days to mass development was 110.3 (range, 18-249 days). In conclusion, this preliminary study suggests that the EPA-registered GonaCon formulation is safe for continued testing in domestic cats, an accidental revaccination should not increase the risk of a vaccine reaction and the EPA-registered formulation effectively elicits a strong humoral immune response. © 2016 Blackwell Verlag GmbH.

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme.

PubMed

Holz, Frank G; Bandello, Francesco; Gillies, Mark; Mitchell, Paul; Osborne, Aaron; Sheidow, Tom; Souied, Eric; Figueroa, Marta S

2013-09-01

Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. The LUMINOUS programme comprises a prospective observational study assessing ranibizumab 'real-world' safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0-0.5%). Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in 'real-life' settings. The 5-year LUMINOUS prospective observational study will address this need.

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme

PubMed Central

Holz, Frank G; Bandello, Francesco; Gillies, Mark; Mitchell, Paul; Osborne, Aaron; Sheidow, Tom; Souied, Eric; Figueroa, Marta S

2013-01-01

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%). Conclusions Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need. PMID:23850682

Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement.

PubMed

Shore, Neal; Tutrone, Ronald; Efros, Mitchell; Bidair, Mohamed; Wachs, Barton; Kalota, Susan; Freedman, Sheldon; Bailen, James; Levin, Richard; Richardson, Stephen; Kaminetsky, Jed; Snyder, Jeffrey; Shepard, Barry; Goldberg, Kenneth; Hay, Alan; Gange, Steven; Grunberger, Ivan

2018-05-01

These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. FT 2.5 mg is a safe and effective transrectal injectable for LT treatment of BPH. FT treated patients also had reduced need for BPH intervention, and reduced incidence of PCa and AUR.

The effectiveness of a mail reminder system for depot medroxyprogesterone injections.

PubMed

Madlon-Kay, D J

1996-04-01

To determine if a mail reminder system leads to an increase in the percentage of depot medroxyprogesterone acetate (Depo-Provera) injections administered on time, the charts of 184 women were reviewed. The reminder postcard included the due dates of both the next medroxyprogesterone injection and the next Papanicolaou test. Timeliness of injections improved with the reminder system from 64% administered on time to 76% (P < .02). Injections given late despite the reminders were late a mean of 8 days. Injections given late before the reminder system began were late a mean of 20 days (P < .05). If injections given during the injection's 14-day "grace" period are included, the on-time rate improved from 87% to 96% with the reminder system (P < .005). The reminder system was not effective in ensuring annual Papanicolaou testing. Vigilance is needed to ensure that women receiving medroxyprogesterone injections also receive timely Papanicolaou testing.

Effect of the helicity injection rate and the Lundquist number on spheromak sustainment

NASA Astrophysics Data System (ADS)

García-Martínez, Pablo Luis; Lampugnani, Leandro Gabriel; Farengo, Ricardo

2014-12-01

The dynamics of the magnetic relaxation process during the sustainment of spheromak configurations at different helicity injection rates is studied. The three-dimensional activity is recovered using time-dependent resistive magnetohydrodynamic simulations. A cylindrical flux conserver with concentric electrodes is used to model configurations driven by a magnetized coaxial gun. Magnetic helicity is injected by tangential boundary flows. Different regimes of sustainment are identified and characterized in terms of the safety factor profile. The spatial and temporal behavior of fluctuations is described. The dynamo action is shown to be in close agreement with existing experimental data. These results are relevant to the design and operation of helicity injected devices, as well as to basic understanding of the plasma relaxation mechanism in quasi-steady state.

A volumetric flow sensor for automotive injection systems

NASA Astrophysics Data System (ADS)

Schmid, U.; Krötz, G.; Schmitt-Landsiedel, D.

2008-04-01

For further optimization of the automotive power train of diesel engines, advanced combustion processes require a highly flexible injection system, provided e.g. by the common rail (CR) injection technique. In the past, the feasibility to implement injection nozzle volumetric flow sensors based on the thermo-resistive measurement principle has been demonstrated up to injection pressures of 135 MPa (1350 bar). To evaluate the transient behaviour of the system-integrated flow sensors as well as an injection amount indicator used as a reference method, hydraulic simulations on the system level are performed for a CR injection system. Experimentally determined injection timings were found to be in good agreement with calculated values, especially for the novel sensing element which is directly implemented into the hydraulic system. For the first time pressure oscillations occurring after termination of the injection pulse, predicted theoretically, could be verified directly in the nozzle. In addition, the injected amount of fuel is monitored with the highest resolution ever reported in the literature.

Rates of fuel discharge as affected by the design of fuel-injection systems for internal-combustion engines

NASA Technical Reports Server (NTRS)

Gelalles, A G; Marsh, E T

1933-01-01

Using the method of weighing fuel collected in a receiver during a definite interval of the injection period, rates of discharge were determined, and the effects noted, when various changes were made in a fuel-injection system. The injection system consisted primarily of a by-pass controlled fuel pump and an automatic injection valve. The variables of the system studied were the pump speed, pump-throttle setting, discharge-orifice diameter, injection-valve opening and closing pressures, and injection-tube length and diameter.

CO2 lidar for measurements of trace gases and wind velocities

NASA Technical Reports Server (NTRS)

Hess, R. V.

1982-01-01

CO2 lidar systems technology and signal processing requirements relevant to measurement needs and sensitivity are discussed. Doppler processing is similar to microwave radar, with signal reception controlled by a computer capable of both direct and heterodyne operations. Trace gas concentrations have been obtained with the NASA DIAL system, and trace gas transport has been determined with Doppler lidar measurements for wind velocity and turbulence. High vertical resolution measurement of trace gases, wind velocity, and turbulence are most important in the planetary boundary layer and in regions between the PBL and the lower stratosphere. Shear measurements are critical for airport operational safety. A sensitivity analysis for heterodyne detection with the DIAL system and for short pulses using a Doppler lidar system is presented. The development of transient injection locking techniques, as well as frequency stability by reducing chirp and catalytic control of closed cycle CO2 laser chemistry, is described.

Novel engineered systems for oral, mucosal and transdermal drug delivery.

PubMed

Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

2013-08-01

Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using cold air for reducing needle-injection pain.

PubMed

Al-Qarqaz, Firas; Al-Aboosi, Mustafa; Al-shiyab, Diala; Al Dabbagh, Ziad

2012-07-01

Pain is associated with skin injections. Reducing injection-associated pain is important especially when multiple injections are needed in difficult areas, such as the palms. We present a new safe application for cold air used in laser therapy. The main objectives of this study are to see whether cold air can reduce needle-injection pain and to evaluate the safety of this new application. Patients undergoing skin injection (n=40) were included. Assessment of pain level using visual analog scale (VAS) was done using cold air and again without cold air in the same patient. Comparison of pain scores was performed. Thirty-three patients had lower VAS scores using cold air. Five patients had worse VAS scores, and two patients did not have any change in their pain score. In the group of patients where injections were made to the palms (n=5), there was even more reduction in VAS scores. There were no significant immediate or delayed side effects. Cold air seems to be useful in reducing needle-injection pain in the majority of patients, especially in the palms. This procedure is safe, apart from immediate tolerable discomfort when used around the nose. © 2012 The International Society of Dermatology.

[Post-marketing safety surveillance of Diemailing Kudiezi injection: real world study in 30 233 cases].

PubMed

Liao, Xing; Yu, Dan-Dan; Xie, Yan-Ming; Zhang, Yun-Ling; He, Yan; Zhang, Yin; Liu, Yan; Yi, Dan-Hui; Wang, Yong-Yan

2017-08-01

This study was aimed to obtain the incidence of adverse drug reaction (ADR) of Diemailing Kudiezi injection, explore its characteristics, related risk factors and application in real world. A prospective single cohort study was conducted from 25 hospitals (including Chinese medicine hospitals and Western medicine hospitals) for 4 years. 30 233 consecutive inpatients using Diemailing Kudiezi injection were observed. Their general information was analyzed by using statistic frequency description. Association rules were used to analyze the correlation between comorbidities or drug combinations; the influential factors for ADRs were initially screened by using cross contingency method and Chi-square test, and then Group LASSAO method was used for further analysis. 54 patients with adverse drug events and 30 patients with ADRs were reported among 30 233 patients, with a total ADR incidence of 0.099%[95%CI (0.06%, 0.13%)]. There were 27 patients identified as the "general" ADR, one patients with "severe" ADR (anaphylactic shock) and two patients with new ADRs. ADR occurred most in 30 min after using Diemailing Kudiezi injection, in a total of 16 patients. The most ADRs were palpitation, vomiting, chills, pruritus and rash, 6 times for each symptom. Diemailing Kudiezi injection was well tolerated in the general population. The overall incidence of adverse reactions was rare, with high safety. However, the real incidence of ADRs may be underestimated in this study, and the blood samples were not obtained for the patients, so further mechanism studies shall be conducted. Copyright© by the Chinese Pharmaceutical Association.

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

PubMed

Behre, Hermann M; Zitzmann, Michael; Anderson, Richard A; Handelsman, David J; Lestari, Silvia W; McLachlan, Robert I; Meriggiola, M Cristina; Misro, Man Mohan; Noe, Gabriela; Wu, Frederick C W; Festin, Mario Philip R; Habib, Ndema A; Vogelsong, Kirsten M; Callahan, Marianne M; Linton, Kim A; Colvard, Doug S

2016-12-01

The development of a safe and effective reversible method of male contraception is still an unmet need. Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Prospective multicentre study. Ten study centers. Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

78 FR 47321 - Determination That CYTOXAN (Cyclophosphamide) for Injection Was Not Withdrawn From Sale for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-05

..., Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's... marketing for reasons other than safety or effectiveness. ANDAs that refer to CYTOXAN (cyclophosphamide) for...

Minimizing the risk of non-vertical, non-sexual HIV infection in children – beyond mother to child transmission

PubMed Central

Cotton, Mark F; Marais, Barend J; Andersson, Monique I; Eley, Brian; Rabie, Helena; Slogrove, Amy L; Dramowski, Angela; Schaaf, Hendrik Simon; Mehtar, Shaheen

2012-01-01

After witnessing an episode of poor injection safety in large numbers of children in a rural under-resourced hospital in Uganda, we briefly review our own experience and that of others in investigating HIV infection in children considered unlikely to be through commonly identified routes such as vertical transmission, sexual abuse or blood transfusion. In the majority of cases, parents are HIV uninfected. The cumulative experience suggests that the problem is real, but with relatively low frequency. Vertical transmission is the major route for HIV to children. However, factors such as poor injection safety, undocumented surrogate breast feeding, an HIV-infected adult feeding premasticated food to a weaning toddler, poor hygienic practice in the home and using unsterilised equipment for minor surgical or traditional procedures are of cumulative concern. PMID:23199798

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

PubMed Central

Sarduy, M R; García, I; Coca, M A; Perera, A; Torres, L A; Valenzuela, C M; Baladrón, I; Solares, M; Reyes, V; Hernández, I; Perera, Y; Martínez, Y M; Molina, L; González, Y M; Ancízar, J A; Prats, A; González, L; Casacó, C A; Acevedo, B E; López-Saura, P A; Alonso, D F; Gómez, R; Perea-Rodríguez, S E

2015-01-01

Background: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. Methods: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. Results: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens. Conclusion: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies. PMID:25880012

Vocal fold medialization in children: injection laryngoplasty, thyroplasty, or nerve reinnervation?

PubMed

Sipp, J Andrew; Kerschner, Joseph E; Braune, Nicole; Hartnick, Christopher J

2007-08-01

To review surgical interventions for pediatric unilateral vocal fold immobility (UVFI). Retrospective medical chart review. Two tertiary academic centers. All children who underwent vocal fold medialization for dysphonia, with or without aspiration, from January 2004 to September 2006. Injection laryngoplasty, ansa cervicalis-recurrent laryngeal nerve anastomosis, or thyroplasty. Age, sex, intervention, etiology, time from onset of UVFI to surgery, subjective success in improving voice, subjective duration of improvement, and complications. Twenty-seven procedures were performed in 15 patients (mean age, 10.6 years). Nineteen injection laryngoplasties, 3 thyroplasties (1 bilateral), 2 ansa cervicalis-recurrent laryngeal nerve reinnervation procedures, 1 adduction arytenoidopexy, and 1 cricothyroid joint subluxation were performed. Causes of UVFI included thoracic surgery in 6 cases (40%), prolonged intubation in 4 (26%), central nervous system neoplasm in 3 (20%), unknown etiology in 1 (7%), and anoxic brain injury in 1 (7%). The mean duration from onset of symptoms to treatment was 47 months. There was 1 surgical complication (postoperative aspiration pneumonia following thyroplasty while the patient was under local anesthesia). Parents reported a satisfactory outcome in all cases. Injection laryngoplasty, thyroplasty, and nerve reinnervation can be performed in pediatric patients with good outcomes and an acceptable safety profile. This article describes the experiences of 2 institutions with phonosurgery for UVFI in children and provides insight into the advantages and disadvantages of each procedure. Prospective studies, with validated quality-of-life measurements, are needed to greater clarify the role of different types of phonosurgery in children with UVFI.

Parents' adherence to pediatric health and safety guidelines: Importance of patient-provider relationships.

PubMed

Fuzzell, Lindsay N; LaJoie, A Scott; Smith, Kyle T; Philpott, Sydney E; Jones, Katherine M; Politi, Mary C

2018-05-01

To examine 1) parent-provider communication about pediatric health/safety guidelines, 2) trust in child's provider, 3) comfort discussing guidelines, 4) agreement with guideline advice, 5) self-efficacy following guidelines, and their impact on guideline adherence. 256 parents of children ages 0-6 completed an online survey about sunscreen use, newborn Vitamin K injections, influenza vaccination, routine vaccination, car seats, infant safe sleep, furniture anchoring, large trampoline use, and firearm safety. Multivariable models regressed: 1) communication about each guideline on parents' corresponding guideline adherence; 2) trust, comfort discussing guidelines, agreement with guideline advice, self-efficacy, on parents' total guideline adherence. Communication about furniture anchoring (OR = 2.26), sunscreen (OR = 5.28), Vitamin K injections (OR = 3.20), influenza vaccination (OR = 13.71), routine vaccination (OR = 6.43), car seats (OR = 6.15), and infant safe sleep (OR = 3.40) related to corresponding guideline adherence (ps < 0.05). Firearm safety communication was not related to adherence (OR = 1.11, n.s.). Trampoline communication related to lower likelihood of trampoline guideline adherence (OR = 0.24, p = 0.001). Agreement with guideline advice (β = 0.35), trust (β = 0.34), self-efficacy (β = 0.45), comfort discussing guidelines (β = 0.35) positively related to total guideline adherence (ps < 0.001). Findings underscore the importance of provider communication about health/safety guidelines. Providers should respectfully engage and build relationships with parents to support health/safety guideline adherence. Copyright © 2018. Published by Elsevier B.V.

Navigation and Image Injection for Control of Bone Removal and Osteotomy Planes in Spine Surgery.

PubMed

Kosterhon, Michael; Gutenberg, Angelika; Kantelhardt, Sven Rainer; Archavlis, Elefterios; Giese, Alf

2017-04-01

In contrast to cranial interventions, neuronavigation in spinal surgery is used in few applications, not tapping into its full technological potential. We have developed a method to preoperatively create virtual resection planes and volumes for spinal osteotomies and export 3-D operation plans to a navigation system controlling intraoperative visualization using a surgical microscope's head-up display. The method was developed using a Sawbone ® model of the lumbar spine, demonstrating feasibility with high precision. Computer tomographic and magnetic resonance image data were imported into Amira ® , a 3-D visualization software. Resection planes were positioned, and resection volumes representing intraoperative bone removal were defined. Fused to the original Digital Imaging and Communications in Medicine data, the osteotomy planes were exported to the cranial version of a Brainlab ® navigation system. A navigated surgical microscope with video connection to the navigation system allowed intraoperative image injection to visualize the preplanned resection planes. The workflow was applied to a patient presenting with a congenital hemivertebra of the thoracolumbar spine. Dorsal instrumentation with pedicle screws and rods was followed by resection of the deformed vertebra guided by the in-view image injection of the preplanned resection planes into the optical path of a surgical microscope. Postoperatively, the patient showed no neurological deficits, and the spine was found to be restored in near physiological posture. The intraoperative visualization of resection planes in a microscope's head-up display was found to assist the surgeon during the resection of a complex-shaped bone wedge and may help to further increase accuracy and patient safety. Copyright © 2017 by the Congress of Neurological Surgeons

Bundling occupational safety with harm reduction information as a feasible method for improving police receptiveness to syringe access programs: evidence from three U.S. cities

PubMed Central

Davis, Corey S; Beletsky, Leo

2009-01-01

Introduction In light of overwhelming evidence that access to sterile injection equipment reduces incidence of injection-attributable bloodborne disease without encouraging drug use, many localities have authorized sterile syringe access programs (SAPs), including syringe exchange and pharmacy-based initiatives. Even where such interventions are clearly legal, many law enforcement officers are unaware of the public health benefits and legal status of these programs and may continue to treat the possession of injection equipment as illegal and program participation as a marker of illegal behavior. Law enforcement practice can impede SAP utilization and may increase the risk of needlestick injury (NSI) among law enforcement personnel. Many SAPs conduct little or no outreach to law enforcement, in part because they perceive law enforcement actors as unreceptive to health-promotion programs targeting drug users. Case description We report on a brief training intervention for law enforcement personnel designed to increase officer knowledge of and positive attitudes towards SAPs by bundling content that addresses officer concerns about infectious disease and occupational safety with information about the legality and public health benefits of these programs. Pilot trainings using this bundled curriculum were conducted with approximately 600 officers in three US cities. Discussion and evaluation Law enforcement officers were generally receptive to receiving information about SAPs through the bundled curriculum. The trainings led to better communication and collaboration between SAP and law enforcement personnel, providing a valuable platform for better harmonization of law enforcement and public health activities targeting injection drug users. Conclusion The experience in these three cities suggests that a harm reduction training curriculum that bundles strategies for increasing officer occupational safety with information about the legality and public health benefits of SAPs can be well received by law enforcement personnel and can lead to better communication and collaboration between law enforcement and harm reduction actors. Further study is indicated to assess whether such a bundled curriculum is effective in changing officer attitudes and beliefs and reducing health risks to officers and injection drug users, as well as broader benefits to the community at large. PMID:19602236

An Approach for the Assessment of System Upset Resilience

NASA Technical Reports Server (NTRS)

Torres-Pomales, Wilfredo

2013-01-01

This report describes an approach for the assessment of upset resilience that is applicable to systems in general, including safety-critical, real-time systems. For this work, resilience is defined as the ability to preserve and restore service availability and integrity under stated conditions of configuration, functional inputs and environmental conditions. To enable a quantitative approach, we define novel system service degradation metrics and propose a new mathematical definition of resilience. These behavioral-level metrics are based on the fundamental service classification criteria of correctness, detectability, symmetry and persistence. This approach consists of a Monte-Carlo-based stimulus injection experiment, on a physical implementation or an error-propagation model of a system, to generate a system response set that can be characterized in terms of dimensional error metrics and integrated to form an overall measure of resilience. We expect this approach to be helpful in gaining insight into the error containment and repair capabilities of systems for a wide range of conditions.

Preliminary analysis of loss-of-coolant accident in Fukushima nuclear accident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su'ud, Zaki; Anshari, Rio

Loss-of-Coolant Accident (LOCA) in Boiling Water Reactor (BWR) especially on Fukushima Nuclear Accident will be discussed in this paper. The Tohoku earthquake triggered the shutdown of nuclear power reactors at Fukushima Nuclear Power station. Though shutdown process has been completely performed, cooling process, at much smaller level than in normal operation, is needed to remove decay heat from the reactor core until the reactor reach cold-shutdown condition. If LOCA happen at this condition, it will cause the increase of reactor fuel and other core temperatures and can lead to reactor core meltdown and exposure of radioactive material to the environmentmore » such as in the Fukushima Dai Ichi nuclear accident case. In this study numerical simulation has been performed to calculate pressure composition, water level and temperature distribution on reactor during this accident. There are two coolant regulating system that operational on reactor unit 1 at this accident, Isolation Condensers (IC) system and Safety Relief Valves (SRV) system. Average mass flow of steam to the IC system in this event is 10 kg/s and could keep reactor core from uncovered about 3,2 hours and fully uncovered in 4,7 hours later. There are two coolant regulating system at operational on reactor unit 2, Reactor Core Isolation Condenser (RCIC) System and Safety Relief Valves (SRV). Average mass flow of coolant that correspond this event is 20 kg/s and could keep reactor core from uncovered about 73 hours and fully uncovered in 75 hours later. There are three coolant regulating system at operational on reactor unit 3, Reactor Core Isolation Condenser (RCIC) system, High Pressure Coolant Injection (HPCI) system and Safety Relief Valves (SRV). Average mass flow of water that correspond this event is 15 kg/s and could keep reactor core from uncovered about 37 hours and fully uncovered in 40 hours later.« less

Preliminary analysis of loss-of-coolant accident in Fukushima nuclear accident

NASA Astrophysics Data System (ADS)

Su'ud, Zaki; Anshari, Rio

2012-06-01

Loss-of-Coolant Accident (LOCA) in Boiling Water Reactor (BWR) especially on Fukushima Nuclear Accident will be discussed in this paper. The Tohoku earthquake triggered the shutdown of nuclear power reactors at Fukushima Nuclear Power station. Though shutdown process has been completely performed, cooling process, at much smaller level than in normal operation, is needed to remove decay heat from the reactor core until the reactor reach cold-shutdown condition. If LOCA happen at this condition, it will cause the increase of reactor fuel and other core temperatures and can lead to reactor core meltdown and exposure of radioactive material to the environment such as in the Fukushima Dai Ichi nuclear accident case. In this study numerical simulation has been performed to calculate pressure composition, water level and temperature distribution on reactor during this accident. There are two coolant regulating system that operational on reactor unit 1 at this accident, Isolation Condensers (IC) system and Safety Relief Valves (SRV) system. Average mass flow of steam to the IC system in this event is 10 kg/s and could keep reactor core from uncovered about 3,2 hours and fully uncovered in 4,7 hours later. There are two coolant regulating system at operational on reactor unit 2, Reactor Core Isolation Condenser (RCIC) System and Safety Relief Valves (SRV). Average mass flow of coolant that correspond this event is 20 kg/s and could keep reactor core from uncovered about 73 hours and fully uncovered in 75 hours later. There are three coolant regulating system at operational on reactor unit 3, Reactor Core Isolation Condenser (RCIC) system, High Pressure Coolant Injection (HPCI) system and Safety Relief Valves (SRV). Average mass flow of water that correspond this event is 15 kg/s and could keep reactor core from uncovered about 37 hours and fully uncovered in 40 hours later.

Evolution of the global use of unsafe medical injections, 2000-2010.

PubMed

Pépin, Jacques; Abou Chakra, Claire Nour; Pépin, Eric; Nault, Vincent

2013-01-01

Since 1999, substantial efforts have been made by the international community to reduce the risks associated with unsafe injections, through ministries of health, international donors, the World Health Organization and the Safe Injection Global Network. The present study attempted to measure the progress, or lack thereof, made over the 2000-2010 decade in reducing unsafe injections in ten regions of the world corresponding to developing and transitional economies. Data about the number of injections per person per year and the proportion of re-use of syringes and needles were obtained for 2010, mainly from population surveys, and compared with previous estimates for 2000 which had used various sources of information including injection safety assessments, population surveys and published studies on injection practices. From 2000 to 2010, in developing countries and transitional economies, the average number of injections per person per year decreased from 3.40 to 2.88, while the proportion of re-use of injection devices dropped from 39.8% to 5.5%. Combining both factors the number of unsafe injections per person per year decreased from 1.35 to 0.16. Even if substantial progress has been made, the Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per person per year. In sub-Saharan Africa and Latin America, people now receive on average only 0.04-0.05 unsafe injections per year. Substantial progress has been made in reducing the number of unsafe injections in developing countries and transitional economies, essentially through a reduction in the re-use of injection devices. In some regions, elimination of unsafe injections might become a reasonable goal.

Protecting Against Damage from Refraction of High Power Microwaves in the DIII-D Tokamak

NASA Astrophysics Data System (ADS)

Lohr, John; Brambila, Rigo; Cengher, Mirela; Chen, Xi; Gorelov, Yuri; Grosnickle, William; Moeller, Charles; Ponce, Dan; Prater, Ron; Torrezan, Antonio; Austin, Max; Doyle, Edward; Hu, Xing; Dormier, Calvin

2017-07-01

Several new protective systems are being installed on the DIII D tokamak to increase the safety margins for plasma operations with injected ECH power at densities approaching cutoff. Inadvertent overdense operation has previously resulted in reflection of an rf beam back into a launcher causing extensive arcing and melt damage on one waveguide line. Damage to microwave diagnostics, which are located on the same side of the tokamak as the ECH launchers, also has occurred. Developing a reliable microwave based interlock to protect the many vulnerable systems in DIII-D has proved to be difficult. Therefore, multiple protective steps have been taken to reduce the risk of damage in the future. Among these is a density interlock generated by the plasma control system, with setpoint determined by the ECH operators based on rf beam trajectories and plasma parameters. Also installed are enhanced video monitoring of the launchers, and an ambient light monitor on each of the waveguide systems, along with a Langmuir probe at the mouth of each launcher. Versatile rf monitors, measuring forward and reflected power in addition to the mode content of the rf beams, have been installed as the last miter bends in each waveguide line. As these systems are characterized, they are being incorporated in the interlock chains, which enable the ECH injection permits. The diagnostics most susceptible to damage from the ECH waves have also been fitted with a variety of protective devices including stripline filters, thin resonant notch filters tuned to the 110 GHz injected microwave frequency, blazed grating filters and shutters. Calculations of rf beam trajectories in the plasmas are performed using the TORAY ray tracing code with input from kinetic profile diagnostics. Using these calculations, strike points for refracted beams on the vacuum vessel are calculated, which allows evaluation of the risk of damage to sensitive diagnostics and hardware.

Protecting against damage from refraction of high power microwaves in the DIII-D tokamak

DOE PAGES

Lohr, John; Brambila, Rigo; Cengher, Mirela; ...

2017-07-24

Here, several new protective systems are being installed on the DIII D tokamak to increase the safety margins for plasma operations with injected ECH power at densities approaching cutoff. Inadvertent overdense operation has previously resulted in reflection of an rf beam back into a launcher causing extensive arcing and melt damage on one waveguide line. Damage to microwave diagnostics, which are located on the same side of the tokamak as the ECH launchers, also has occurred. Developing a reliable microwave based interlock to protect the many vulnerable systems in DIII-D has proved to be difficult. Therefore, multiple protective steps havemore » been taken to reduce the risk of damage in the future. Among these is a density interlock generated by the plasma control system, with setpoint determined by the ECH operators based on rf beam trajectories and plasma parameters. Also installed are enhanced video monitoring of the launchers, and an ambient light monitor on each of the waveguide systems, along with a Langmuir probe at the mouth of each launcher. Versatile rf monitors, measuring forward and reflected power in addition to the mode content of the rf beams, have been installed as the last miter bends in each waveguide line. As these systems are characterized, they are being incorporated in the interlock chains, which enable the ECH injection permits. The diagnostics most susceptible to damage from the ECH waves have also been fitted with a variety of protective devices including stripline filters, thin resonant notch filters tuned to the 110 GHz injected microwave frequency, blazed grating filters and shutters. Calculations of rf beam trajectories in the plasmas are performed using the TORAY ray tracing code with input from kinetic profile diagnostics. Using these calculations, strike points for refracted beams on the vacuum vessel are calculated, which allows evaluation of the risk of damage to sensitive diagnostics and hardware.« less

Protecting against damage from refraction of high power microwaves in the DIII-D tokamak

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohr, John; Brambila, Rigo; Cengher, Mirela

Here, several new protective systems are being installed on the DIII D tokamak to increase the safety margins for plasma operations with injected ECH power at densities approaching cutoff. Inadvertent overdense operation has previously resulted in reflection of an rf beam back into a launcher causing extensive arcing and melt damage on one waveguide line. Damage to microwave diagnostics, which are located on the same side of the tokamak as the ECH launchers, also has occurred. Developing a reliable microwave based interlock to protect the many vulnerable systems in DIII-D has proved to be difficult. Therefore, multiple protective steps havemore » been taken to reduce the risk of damage in the future. Among these is a density interlock generated by the plasma control system, with setpoint determined by the ECH operators based on rf beam trajectories and plasma parameters. Also installed are enhanced video monitoring of the launchers, and an ambient light monitor on each of the waveguide systems, along with a Langmuir probe at the mouth of each launcher. Versatile rf monitors, measuring forward and reflected power in addition to the mode content of the rf beams, have been installed as the last miter bends in each waveguide line. As these systems are characterized, they are being incorporated in the interlock chains, which enable the ECH injection permits. The diagnostics most susceptible to damage from the ECH waves have also been fitted with a variety of protective devices including stripline filters, thin resonant notch filters tuned to the 110 GHz injected microwave frequency, blazed grating filters and shutters. Calculations of rf beam trajectories in the plasmas are performed using the TORAY ray tracing code with input from kinetic profile diagnostics. Using these calculations, strike points for refracted beams on the vacuum vessel are calculated, which allows evaluation of the risk of damage to sensitive diagnostics and hardware.« less

Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee.

PubMed

Altman, Roy D; Bedi, Asheesh; Karlsson, Jon; Sancheti, Parag; Schemitsch, Emil

2016-08-01

Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee. To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA. Meta-analysis. A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics. A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation-derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation-derived HA had a significantly smaller incidence of effusion than did avian-derived HA. Biological fermentation-derived HA demonstrated fewer acute flare-ups at the injection site than did avian-derived HA products, while high-molecular-weight products demonstrated the highest rate of injection site flare-up. Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety-factors that may influence selection an IA-HA product for OA of the knee. © 2015 The Author(s).

Comparison of a RELAP5/MOD2 posttest calculation to the data during the recovery portion of a semiscale single-tube steam generator tube rupture experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, J.C.

This report discusses the comparisons of a RELAP5 posttest calculation of the recovery portion of the Semiscale Mod-2B test S-SG-1 to the test data. The posttest calculation was performed with the RELAP5/MOD2 cycle 36.02 code without updates. The recovery procedure that was calculated mainly consisted of secondary feed and steam using auxiliary feedwater injection and the atmospheric dump valve of the unaffected steam generator (the steam generator without the tube rupture). A second procedure was initiated after the trends of the secondary feed and steam procedure had been established, and this was to stop the safety injection that had beenmore » provided by two trains of both the charging and high pressure injection systems. The Semiscale Mod-2B configuration is a small scale (1/1705), nonnuclear, instrumented, model of a Westinghouse four-loop pressurized water reactor power plant. S-SG-1 was a single-tube, cold-side, steam generator tube rupture experiment. The comparison of the posttest calculation and data included comparing the general trends and the driving mechanisms of the responses, the phenomena, and the individual responses of the main parameters.« less

Diffusion, spread, and migration of botulinum toxin.

PubMed

Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

2013-11-01

Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. © 2013 International Parkinson and Movement Disorder Society.

OSIRIS and SOMBRERO Inertial Fusion Power Plant Designs, Volume 2: Designs, Assessments, and Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meier, W. R.; Bieri, R. L.; Monsler, M. J.

1992-03-01

This is a comprehensive design study of two Inertial Fusion Energy (IFE) electric power plants. Conceptual designs are presented for a fusion reactor (called Osiris) using an induction-linac heavy-ion beam driver, and another (called SOMBRERO) using a KrF laser driver. The designs covered all aspects of IFE power plants, including the chambers, heat transport and power conversion systems, balance-of-plant facilities, target fabrication, target injection and tracking, as well as the heavy-ion and KrF drivers. The point designs were assessed and compared in terms of their environmental & safety aspects, reliability and availability, economics, and technology development needs.

Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

PubMed

Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

2017-08-01

The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright © 2017. Published by Elsevier B.V.

Long-term suppression of ocular neovascularization by intraocular injection of biodegradable polymeric particles containing a serpin-derived peptide.

PubMed

Shmueli, Ron B; Ohnaka, Masayuki; Miki, Akiko; Pandey, Niranjan B; Lima e Silva, Raquel; Koskimaki, Jacob E; Kim, Jayoung; Popel, Aleksander S; Campochiaro, Peter A; Green, Jordan J

2013-10-01

Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

PubMed

Gilbert, Mark R; Young, VyVy N; Smith, Libby J; Rosen, Clark A

2018-01-04

Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. This is a retrospective review and projected cost savings analysis. Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness. Copyright © 2018. Published by Elsevier Inc.

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Thermal-hydraulic modeling needs for passive reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, J.M.

1997-07-01

The U.S. Nuclear Regulatory Commission has received an application for design certification from the Westinghouse Electric Corporation for an Advanced Light Water Reactor design known as the AP600. As part of the design certification process, the USNRC uses its thermal-hydraulic system analysis codes to independently audit the vendor calculations. The focus of this effort has been the small break LOCA transients that rely upon the passive safety features of the design to depressurize the primary system sufficiently so that gravity driven injection can provide a stable source for long term cooling. Of course, large break LOCAs have also been considered,more » but as the involved phenomena do not appear to be appreciably different from those of current plants, they were not discussed in this paper. Although the SBLOCA scenario does not appear to threaten core coolability - indeed, heatup is not even expected to occur - there have been concerns as to the performance of the passive safety systems. For example, the passive systems drive flows with small heads, consequently requiring more precision in the analysis compared to active systems methods for passive plants as compared to current plants with active systems. For the analysis of SBLOCAs and operating transients, the USNRC uses the RELAP5 thermal-hydraulic system analysis code. To assure the applicability of RELAP5 to the analysis of these transients for the AP600 design, a four year long program of code development and assessment has been undertaken.« less

Enoxaparin Injection

MedlinePlus

... as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in ...

Liver Disease

MedlinePlus

... and don't share needles used to inject drugs. Use a condom during sex. If you choose to have tattoos or body piercings, be picky about cleanliness and safety when selecting a shop. Get vaccinated. If you're at increased risk ...

49 CFR 192.171 - Compressor stations: Additional safety equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... operates with pressure gas injection must be equipped so that stoppage of the engine automatically shuts off the fuel and vents the engine distribution manifold. (e) Each muffler for a gas engine in a...

49 CFR 192.171 - Compressor stations: Additional safety equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... operates with pressure gas injection must be equipped so that stoppage of the engine automatically shuts off the fuel and vents the engine distribution manifold. (e) Each muffler for a gas engine in a...

A Safety Study on Intrathecal Delivery of Autologous Mesenchymal Stromal Cells in Rabbits Directly Supporting Phase I Human Trials

PubMed Central

Chen, Bingkun K.; Staff, Nathan P.; Knight, Andrew M.; Nesbitt, Jarred J.; Butler, Greg W.; Padley, Douglas J.; Parisi, Joseph E.; Dietz, Allan B.; Windebank, Anthony J.

2014-01-01

Background There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs – either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model. Methods Autologous adipose-derived MSCs (or a-CSF) were delivered intrathecally, either with single or repeated injections into the foramen magnum of healthy rabbits, and monitored for 4 and 12 weeks, respectively. Results Rabbits tolerated injections well and no definitive MSC-related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count (CBC) data were normal and there were no differences in CSF IL-6 levels in all groups tested. Discussion Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study has supported two successful Investigational New Drug (IND) applications to the FDA, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy. PMID:25413276

Experimental iron-inactivated Pasteurella multocida A: 1 vaccine adjuvanted with bacterial DNA is safe and protects chickens from fowl cholera.

PubMed

Herath, Chitra; Kumar, Pankaj; Singh, Mithilesh; Kumar, Devender; Ramakrishnan, Saravanan; Goswami, Tapas Kumar; Singh, Ajit; Ram, G C

2010-03-08

Fowl cholera is a serious problem in large and small scale poultry production. The present study describes the development and testing of an inactivated whole-cell, low-cost, safe, and effective vaccine for fowl cholera based on a previous work (Vaccine 23:5590-5598). Pasteurella multocida A: 1 grown in the presence of low FeCl(3) concentrations, inactivated with higher concentrations of FeCl(3), and adjuvanted with bacterial DNA from P. multocida B: 2 containing immunostimulatory CpG motifs protect chickens with a lethal P. multocida A: 1 challenge. Chickens were immunized with two whole-cell inactivated vaccine doses at 4 weeks apart and challenged 4 weeks after booster immunization. Experimental vaccines were pure, easy injectable, and caused very little distress in chickens due to their aqueous consistency. Vaccines and bacterial DNA (bDNA) posed no safety problems when chickens were injected subcutaneously (s.c.) with a single, double, and overdose of these preparations. Immunized chickens produced systemic IgY antibodies (Ab) responses and vaccine adjuvanted with bDNA protected 100% chickens from lethal intrapertoneal (i.p.) P. multocida A: 1 challenge. This work suggests that use of bDNA as an adjuvant can improve the cost-effectiveness of inactivated veterinary vaccines for their use in developing countries. Our future studies will focus on safety and potency evaluation of experimental and current vaccines using bDNA as an adjuvant. Copyright 2010 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial.

PubMed

Groome, Michelle J; Koen, Anthonet; Fix, Alan; Page, Nicola; Jose, Lisa; Madhi, Shabir A; McNeal, Monica; Dally, Len; Cho, Iksung; Power, Maureen; Flores, Jorge; Cryz, Stanley

2017-08-01

Efficacy of live oral rotavirus vaccines is reduced in low-income compared with high-income settings. Parenteral non-replicating rotavirus vaccines might offer benefits over oral vaccines. We assessed the safety and immunogenicity of the P2-VP8-P[8] subunit rotavirus vaccine at different doses in South African toddlers and infants. This double-blind, randomised, placebo-controlled, dose-escalation trial was done at a single research unit based at a hospital in South Africa in healthy HIV-uninfected toddlers (aged 2 to <3 years) and term infants (aged 6 to <8 weeks, without previous rotavirus vaccination). Block randomisation (computer-generated, electronic allocation) was used to assign eligible toddlers (in a 6:1 ratio) and infants (in a 3:1 ratio) in each dose cohort (10 μg, followed by 30 μg, then 60 μg if doses tolerated) to parenteral P2-VP8-P[8] subunit rotavirus or placebo injection. The two highest tolerated doses were then assessed in an expanded cohort (in a 1:1:1 ratio). Parents of participants and clinical, data, and laboratory staff were masked to treatment assignment. P2-VP8-P[8] vaccine versus placebo was assessed first in toddlers (single injection) and then in infants (three injections 4 weeks apart). The primary safety endpoints were local and systemic reactions within 7 days after each injection, adverse events within 28 days after each injection, and all serious adverse events, assessed in toddlers and infants who received at least one dose. In infants receiving all study injections, primary immunogenicity endpoints were anti-P2-VP8-P[8] IgA and IgG and neutralising antibody seroresponses and geometric mean titres 4 weeks after the third injection. This trial is registered at ClinicalTrials.gov, number NCT02109484. Between March 17, 2014, and Sept 29, 2014, 42 toddlers (36 to vaccine and six to placebo) and 48 infants (36 to vaccine and 12 to placebo) were enrolled in the dose-escalation phase, in which the 30 μg and 60 μg doses where found to be the highest tolerated doses. A further 114 infants were enrolled in the expanded cohort between Nov 3, 2014, and March 20, 2015, and all 162 infants (12 assigned to 10 μg, 50 to 30 μg, 50 to 60 μg, and 50 to placebo) were included in the safety analysis. Serum IgA seroresponses were observed in 38 (81%, 95% CI 67-91) of 47 infants in the 30 μg group and 32 (68%, 53-81) of 47 in the 60 μg group, compared with nine (20%, 10-35) of 45 in the placebo group; adjusted IgG seroresponses were seen in 46 (98%, 89-100) of 47 infants in the 30 μg group and 47 (100%; 92-100) of 47 in the 60 μg group, compared with four (9%, 2·5-21) of 45 in the placebo group; and adjusted neutralising antibody seroresponses against the homologous Wa-strain were seen in 40 (85%, 72-94) of 47 infants in both the 30 μg and 60 μg groups, compared with three (7%, 1·4-18) of 45 participants in the placebo group. Solicited reactions following any injection occurred with similar frequency and severity in participants receiving vaccine and those receiving placebo. Unsolicited adverse events were mostly mild and occurred at a similar frequency between groups. Eight serious adverse events (one with placebo, two with 30 μg, and five with 60 μg) occurred in seven infants within 28 days of any study injection, none of which were deemed related to study treatment. The parenteral P2-VP8-P[8] vaccine was well tolerated and immunogenic in infants, providing a novel approach to vaccination against rotavirus disease. On the basis of these results, a phase 1/2 trial of a trivalent P2-VP8 (P[4], P[6], and P[8]) subunit vaccine is underway at three sites in South Africa. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

30 CFR 36.22 - Fuel-injection system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fuel-injection system. 36.22 Section 36.22... EQUIPMENT Construction and Design Requirements § 36.22 Fuel-injection system. This system shall be so.... Provision shall be made for convenient adjustment of the maximum fuel-injection rate to that required for...

30 CFR 36.22 - Fuel-injection system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fuel-injection system. 36.22 Section 36.22... EQUIPMENT Construction and Design Requirements § 36.22 Fuel-injection system. This system shall be so.... Provision shall be made for convenient adjustment of the maximum fuel-injection rate to that required for...

30 CFR 36.22 - Fuel-injection system.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Fuel-injection system. 36.22 Section 36.22... EQUIPMENT Construction and Design Requirements § 36.22 Fuel-injection system. This system shall be so.... Provision shall be made for convenient adjustment of the maximum fuel-injection rate to that required for...

30 CFR 36.22 - Fuel-injection system.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fuel-injection system. 36.22 Section 36.22... EQUIPMENT Construction and Design Requirements § 36.22 Fuel-injection system. This system shall be so.... Provision shall be made for convenient adjustment of the maximum fuel-injection rate to that required for...

30 CFR 36.22 - Fuel-injection system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fuel-injection system. 36.22 Section 36.22... EQUIPMENT Construction and Design Requirements § 36.22 Fuel-injection system. This system shall be so.... Provision shall be made for convenient adjustment of the maximum fuel-injection rate to that required for...

Using anti-VEGF McAb and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer.

PubMed

Chen, Jing; Wu, Hua; Han, Deyan; Xie, Changsheng

2006-01-18

To study the biodistribution of a new radioimmunoconjugate-131I-anti-VEGF monoclonal antibody (Sc-7269)-Dextran Magnetic Nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Tumor Growth Delay (TGD) and tumor inhibition rate were observed as antitumor effect. Peripheral white blood cells counts and the loss of body weight were tested as an indicator of systemic toxicity. The results suggests that the radioimmunotherapy of intratumoral injection of 131I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a 'carrier system' may be a highly potential approach in the treatment of other kind of tumors.

Treatment of Lipoma by Injection Lipolysis

PubMed Central

Nanda, Soni

2011-01-01

Injection lipolysis or lipodissolve is the practice of injecting phosphatidyl choline/ sodium deoxycholate (PDC/DC) compounds in the subcutaneous fat. Though this practice is being used extensively for nonsurgical contouring of body and dissolving localized collections of excess fat, it's use as a treatment modality for lipomas needs further evaluation. We present a case where this technique was used for treating a lipoma, with no recurrence after 9 months of follow up. Injection lipolysis as a treatment modality for lipomas needs to be evaluated for safety and efficacy in trials on larger population. This could prove to be a very valuable adjunct to the current practice of excision, if done by a trained person in a properly selected patient. Also the side effects and the controversies regarding this procedure have been discussed in detail in the present paper. PMID:21976907

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

The acceptability of an injectable, once-a-month male contraceptive in China.

PubMed

Zhang, Liying; Shah, Iqbal H; Liu, Yunrong; Vogelsong, Kirsten M; Zhang, Lihong

2006-05-01

An acceptability study of an injectable preparation of the synthetic steroid testosterone undecanoate as a once-a-month male contraceptive method was carried out concurrently with, but independently from, a clinical safety and efficacy trial of this preparation in China, from 1997 to 1999. Three hundred eight men, the entire group of volunteers enrolled in the clinical trial, were interviewed using a structured questionnaire. In addition, 24 sessions of focus group discussions and 54 in-depth interviews were conducted with a broad range of stakeholders, including men enrolled in the trial and their wives, potential users, service providers, principal investigators of the six participating clinical trial centers, provincial and national policy makers, and experts engaged in research and development of male methods of contraception. Overall, men found the regimen to be acceptable, and most reported no change or an improvement in their well-being as a result of participating in the clinical study. The frequency of the injections, monthly semen analyses and the need to use another contraceptive method during the period of sperm suppression were reported inconveniences of the trial. Further research is needed to assess the long-term safety, continuation rates, satisfaction among users and issues related to service delivery.

Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine: an open-label phase I clinical trial.

PubMed

Hu, Yue-Mei; Huang, Shou-Jie; Chu, Kai; Wu, Ting; Wang, Zhong-Ze; Yang, Chang-Lin; Cai, Jia-Ping; Jiang, Han-Min; Wang, Yi-Jun; Guo, Meng; Liu, Xiao-Hui; Huang, Hong-Jiang; Zhu, Feng-Cai; Zhang, Jun; Xia, Ning-Shao

2014-01-01

An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.

Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

PubMed

Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

2017-10-13

The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhaled Insulin: A Clinical and Historical Review.

PubMed

Chan, Jason; Cheng-Lai, Angela

Insulin is the most effective blood glucose lowering agent and remains one of the cornerstones of diabetes management. However, many individuals with diabetes are either reluctant to initiate or are nonadherent to their insulin therapy for various reasons, including fear of frequent injections. Technosphere Insulin (TI) is a novel inhaled insulin powder that is approved by the United States Food and Drug Administration for the management of diabetes. The results from 2 phase III clinical trials have shown that TI was noninferior to subcutaneous insulin aspart and superior to inhaled placebo in lowering HbA1c in patients with diabetes mellitus types 1 and 2, respectively. Across both studies, TI appears to be generally well tolerated, with the most common adverse events being hypoglycemia and cough. However, long-term pulmonary safety concerns have not been addressed and additional studies are needed. Overall, TI appears to be a promising noninvasive prandial insulin alternative for individuals with diabetes who are at risk for medication nonadherence due to aversion to frequent injections. This article provides a review of the historical development of TI, its safety and efficacy data, and its advantages and disadvantages over traditional injectable insulins.

Fascian.

PubMed

Burres, Steve

2004-05-01

Fascian is preserved particulate fascia derived from the gastrocnemious fascia that extends from the Achilles tendon. Over 50,000 syringes of material have been sold to physicians over the past six years with an impeccable safety record. The material has been used for wrinkles, scars, fat atrophy, diffuse depressions, paralyzed lips and tongues, nasolabial folds, cellulite, and other problems. Solid fascia grafts are routinely replaced with native collagen and a similar effect may be achieved with Fascian, especially after repeat injections. The FDA classifies the material as a tissue product, so injections may be made anywhere in the human body at the physician's discretion. Injections may last from a few months to permanently, depending on the volume of material, location, particle size, skin layer, and technique.

Aripiprazole Long-Acting Injectable for Maintenance Treatment of Bipolar I Disorder in Adults.

PubMed

Aggarwal, Arpit; Schrimpf, Lindsey; Lauriello, John

2018-01-01

Bipolar I disorder is a serious and disabling psychiatric illness. It is associated with a significant reduction in quality of life and an increased risk for suicide. Pharmacotherapy is essential for both the acute and maintenance treatment of bi-polar I disorder. While multiple oral medications are recommended for the maintenance treatment, there are not many long-acting injectable medications approved for this indication. New treatments that would improve patient adherence have the potential for decreasing relapses and improving patients' ability to remain functional members of society. In this paper we discuss the available data for safety and efficacy of aripiprazole long-acting injectable in bipolar disorder.