Assessing the Utility of In-Line Intravenous Infusion Filters.

The use of in-line filters to remove fibrous material in the administration of intravenous fluids dates to the early 1830's. Following advancements in therapeutic interventions, high volume fluid support and parenterally administered drugs and biologic preparations, some observers are calling for a routine use of bedside filtration. Unfortunately, the assessment of filter components, their interaction and compatibility with the drug product, and the impact of use on clinical outcomes cannot be conducted by a single entity. Recommendations for use are often predicated upon fragmented and incomplete information. The current challenges in evaluating the benefit/risk profile for the use of in-line filters should not be ignored. While there are select instances showing well-defined therapeutic settings where in-line filtration of intravenous infusions would likely provide an additional safety margin and hence, net benefit, the majority of observational studies to date fail to provide sufficient scientific support for broad-based routine use. While infusion set filters are appropriate where expert opinion is well corroborated by scientific evidence, the general and routine use of filters used during parenteral administration cannot be supported by substantive studies and should not be routinely utilized. Ultimately, the determination falls to a healthcare provider with the information available at-hand.

Conducting Clinical Risk Assessments for Visible Particulate Matter in Parenteral Preparations.

Visible particulate matter in injectables presents one important question for consideration: "What are the potential implications to the patient?" The risks of visible particulate matter to patient safety have been comprehensively reviewed elsewhere. However, the methods used to assess and characterize the risks have been explained with various degrees of specificity and supporting rationale. To date, the assessment process lacks the necessary consensus to permit a more standardized and consistent approach to evaluate the potential patient risks.The purpose of this commentary is to provide one model that might be used to evaluate the three most relevant factors impacting the risk of injections containing particulate matter: the source of the particle, particle-specific attributes, and characteristics of the intended patient population. Each of these factors is considered with a focus on the more important aspects that might be relevant to imposing untoward risk. The discussion also includes the importance of differentiating the concepts of risk assessment from risk acceptance when establishing criticality levels for product attributes.LAY ABSTRACT: Pharmaceutical products intended for injection or infusion may contain particles that can emanate from different sources. Some particles, such as suspensions, are intended. Others are not, and those particles are the subject of rigorous manufacturing process controls to limit their presence and reject units that might contain visible defects. However, no technology exists that can prevent or eliminate all particles from these products. As a result, comprehensive risk assessments must be conducted to identify the capability of manufacturing systems to limit particles and detect and reject atypical units. An essential component of this strategy includes understanding the potential impact that injected or infused particles might have to a patient receiving these medications. The purpose of this paper is to provide one approach that clinicians might use to conduct that risk assessment by discussing the important aspects of the source of the particle, its characteristics (such as size or composition), and the relevant patient factors such as the illness being treated or other medical conditions that might impact the risk to these patients if particles are injected or infused.

Screen-detected subsolid pulmonary nodules: long-term follow-up and application of the PanCan lung cancer risk prediction model.

OBJECTIVE: To report the long-term follow-up of subsolid nodules (SSNs) detected in participants of a prospective low-dose CT lung cancer screening cohort, and to investigate the utility of the PanCan model in stratifying risk in baseline SSNs. METHODS: Participants underwent a baseline scan, two annual incidence scans and further follow-up scans for the detected nodules. All SSNs underwent a minimum of 2 years of follow-up (unless resolved or resected). Risk of malignancy was estimated using the PanCan model; discrimination [area under the receiver-operating characteristic curve (AUC)] and calibration (Hosmer-Lemeshow goodness-of-fit test) were assessed. The Mann-Whitney U-Wilcoxon test was used to compare estimated risk between groups. RESULTS: 70 SSNs were detected in 41 (16.0%) out of 256 total participants. Median follow-up period was 25.5 months (range 2.0-74.0 months). 29 (41.4%) SSNs were transient. Five (7.1%) SSNs were resected, all found to be Stage I lung adenocarcinoma, including one SSN stable in size for 3.0 years before growth was detected. The PanCan model had good discrimination for the 52 baseline SSNs (AUC = 0.89; 95% confidence interval 0.76-1); the Hosmer-Lemeshow goodness-of-fit test was non-significant (p = 0.27). Estimated risk was significantly higher in the baseline SSNs found to be cancer vs those not found to be cancer after 2-6 years of follow-up (p < 0.01). CONCLUSION: Our findings support a long-term follow-up approach for screen-detected SSNs for 3 years or longer. The PanCan model appeared discriminatory and well calibrated in this cohort. ADVANCES IN KNOWLEDGE: The PanCan model may have utility in identifying low-risk SSNs which could be followed with less frequent CT scans.

A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.

Imaging of the pleura.

Imaging is integral to the investigation and management of pleural disease. This article addresses some of the important contributions of imaging to pleural disease, concentrating on ultrasonography, multislice computed tomography, magnetic resonance imaging, and positron-emission tomography combined with computed tomography.

Effects of prenatal cocaine exposure on latent inhibition in 1-year-old female rats.

Prenatal cocaine exposure has been shown to produce attentional changes in human infants and children, as well as in preweanling and young adult animals. The aim of the current study was to determine whether attentional effects of in utero cocaine exposure persist into middle adulthood. Sprague-Dawley dams received twice-daily subcutaneous (sc) administration of either 20 mg/kg cocaine HCl or 0.9% saline vehicle from Gestational Day 8 to 20. Saline-injected dams were pair-fed to cocaine-injected subjects during prenatal treatment. A second control group received no treatment and had ad lib access to food. One-year-old female offspring were tested for latent inhibition (LI) of a context conditioning task, using freezing and vertical nose crossing (VNC) as behavioral measures of fear. Although freezing did not reveal any differences between prenatal treatment groups, a cocaine-dependent reduction in baseline VNC indicated that cocaine-exposed adult offspring were less explorative than controls. In addition, cocaine-exposed animals showed enhanced LI as measured by greater levels of VNC than controls in the context preexposed condition of the task. These results provide insight into the nature of attentional contributions to prenatal cocaine effects on learning and indicate that such effects persist well into adulthood.

Prenatal cocaine effects on fear conditioning: exaggeration of sex-dependent context extinction.

Prenatal cocaine exposure results in deficits in sensory preconditioning, discrimination reversal, and spatial navigation, tasks that require input from the hippocampus. However, there are no previous studies concerning prenatal cocaine effects on contextual fear conditioning, another hippocampal-dependent task. The present experiments tested whether chronic subcutaneous administration of 40 mg/kg of cocaine HCl to pregnant rats, from gestational day (GD) 8 through 20 would lead to disruption of contextual fear conditioning in adult male and female offspring. Offspring of saline-injected/pair-fed and untreated dams served as controls. Experiment 1 used a one-trial context conditioning preparation. Rats received a 2-s, 1-mA footshock in either the test context or a novel context, or received no shock on the day prior to the no-shock test. Defecation and freezing were measures of fear. Experiment 2 used a multiple measures protocol to optimize detection of prenatal treatment effects and was preceded by an open-field test. Rats received a 2-s, 0.8-mA footshock or no shock once daily over 4 days of conditioning. During 3 days of extinction, access to an adjacent chamber enabled the observation of four additional measures of fear: side crossing, latency, nose crossing, and side-differential. There were gender-dependent effects of conditioning on freezing and the four added measures of fear. Males showed higher levels of context conditioning and extinguished more slowly than females. The measures of nose crossing and side-differential revealed that prenatal cocaine exposure exaggerated gender-specific effects of context conditioning. The effects of prenatal cocaine exposure on context extinction are sexually dimorphic.

Inhibition of Patulin Production with the Insecticide Naled.

Patulin is a wide spectrum biocide produced by several species of Aspergillus , Penicillium and Byssochlamys , and is a potentially important mycotoxin that may be ingested by man. The effect of the insecticide naled on fungal growth and patulin production was evaluated using three concentrations (1, 10, and 100 mg/l, ppm) and several application times both before inoculation and during growth of the fungus. If added before inoculation, naled at 100 mg/l completely inhibited mycelial growth of Penicillium urticae for 15 days and patulin production for 30 days. When the concentration was decreased to 10 mg/l, and the insecticide added at the time of inoculation, patulin production was inhibited by 59%. If 100 mg of naled/1 was added between 3 and 6 days after fungal growth was visible, patulin production was inhibited by more than 50%. If the insecticide was added at this same concentration to cultures older than 6 days, patulin production was inhibited by 25-35%. Production of patulin in apples was inhibited by 76% and tissue damage inhibited by 43% when 100 mg of naled/1 was applied to apples before their inoculation and storage at 25 C. Naled was highly effective in inhibiting patulin production and showed long-term activity. However, naled completely inhibited patulin production only when applied before growth of the fungus.