Benchmark dose approaches in chemical health risk assessment in relation to number and distress of laboratory animals

Use of benchmark dose (BMD) approaches is expected to increase substantially, with growing awareness among researchers and inclusion in regulatory testing guidance documents such as REACH. The BMD approach has clear advantages over the No-Observed-Adverse-Effect-Level (NOAEL) approach in defining toxicological thresholds, risk levels, and points of departure as the basis for setting guidance and limit values. Several aspects of the BMD may increase the use of laboratory animals; the optimal number of dose groups for BMD calculation is between five and ten, rather than the current standard of four; also, experiments with more animals will result in narrow confidence intervals. However, this paper presents several counterarguments suggesting that design of experiments suited for BMD analyses might be used to decrease the distress and use of laboratory animals. If experiments are performed with unequal group size, with fewer animals in the high response dose groups and more animals close to toxicological threshold, the aggregated distress might be reduced. In addition, there is a need to evaluate how the total number of animals affects the quality of BMD (e.g. in terms of confidence intervals). Development of strategies for optimal design of experiments requires tools which evaluate experimental designs from an ethical perspective; a concept of distress-adjusted number of animals is suggested.     

Proportion of deproteinized bovine bone and autogenous bone affects bone formation in the treatment of calvarial defects in rabbits

This study assessed new bone formation generated using three different proportions of autogenous bone (AB) and deproteinized bovine bone (DBB). Thirty bicortical skull defects were prepared in 15 rabbits, divided into 3 groups: Group 1, critical size defect (CSD) versus AB as controls; Group 2, DBB versus a composite of AB and DBB using a proportion of 1:1; and Group 3, a composite of AB and DBB using a proportion of 1:2 versus a proportion of 1:4. After 8 weeks, radiographic evaluation was assessed using densitometry and new bone formation by histomorphometry. The mean optical density of the CSD (0.108 ± 0.238) and AB (0.352 ± 0.161) groups differed significantly from the DBB group (1.044 ± 0.093) and the groups using a proportion of 1:1 (0.905 ± 0.078), 1:2 (0.865 ± 0.294) and 1:4 (0.867 ± 0.304). Histomorphometry revealed a higher percentage of new bone in the AB group (30.223 ± 16.722) than in the groups using proportions of 1:2 (22.639 ± 5.659), 1:1 (20.929 ± 6.169), 1:4 (9.621 ± 2.400), DBB (14.441 ± 2.742) and CSD (10.645 ± 8.868), respectively. The 1:2 group had significantly higher bone content than the 1:4 group. The proportions of 1:1 and 1:2 resulted in greater bone formation than the proportion of 1:4, DBB and CSD.     

Silodosin: A selective α1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia

Background: Silodosin is a new α₁-adrenergic receptor antagonist that is selective for the α_1A-adrenergic receptor. It was approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).Objective: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of silodosin in adult male patients with BPH.Methods: A search of MEDLINE (1950–October 8, 2009), International Pharmaceutical Abstracts (1970–October 8, 2009), and the Iowa Drug Information Service database (1966–October 8, 2009) was conducted using the terms silodosin, KMD-3213, benign prostatic hyperplasia, and α₁-adrenergic receptor antagonist. Reports of research and review articles published in English were identified and evaluated, and the bibliographies of these articles were reviewed for additional relevant publications. A search of the FDA Web site was performed, and abstracts and posters presented at scientific meetings of the American Urological Association were reviewed.Results: By antagonizing α_1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the LUT. Silodosin has greater affinity for the α_1A-adrenergic receptor than for the α_1B-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by α_1B blockade. In 3 controlled clinical studies in patients with BPH-related LUTS (1 published; 2 presented in the prescribing information and published in a pooled analysis), patients receiving silodosin at a total daily dose of 8 mg had significant improvements in the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q_max) compared with those receiving placebo (both, P < 0.05). The most commonly reported adverse effect was abnormal or retrograde ejaculation (>22%), and the incidence of orthostatic hypotension was low (<3%).Conclusions: In the small number of clinical trials reviewed, silodosin was associated with significant reductions in IPSS and Q_max compared with placebo. To determine whether silodosin's selectivity for the α_1A-adrenergic receptor translates into a clinical advantage relative to other available agents, long-term studies evaluating the comparative efficacy and tolerability of silodosin and other α₁-blockers (specifically tamsulosin) are necessary.     

LOINC® Codes for Hospital Information Systems Documents: A Case Study

Hospital Information Systems (HIS) handle a large number of different types of documents. Exchange and analysis of data from different HIS is facilitated by the use of standardized codes to identify document types. HL7's Clinical Document Architecture (CDA) uses LOINC (logical observation identifiers names and Codes) codes for clinical documents. The authors assessed the coverage of LOINC codes for document types in a German HIS. The authors analyzed document types that occurred more than 10 times in approximately 1.3 million documents in a commercial HIS at a major German University Hospital. Document types were mapped manually to LOINC using the Regenstrief LOINC Mapping Assistant (RELMA). Each document type was coded by two physicians. In case of discrepancies a third expert was consulted to reach consensus. For 76 of 86 document categories a LOINC code was identified, but for 38 of these categories, the LOINC code was not specific as deemed necessary. More than 93% of our local HIS documents had local document types that could be assigned a LOINC code.     

Nurses' Opinions on Appropriate Administration of PRN Range Opioid Analgesic Orders for Acute Pain

The use of “as needed” or “pro re nata” (PRN) range opioid analgesic orders is a common clinical practice in the management of acute pain, designed to provide flexibility in dosing to meet an individual's unique needs. Range orders enable necessary adjustments in doses based on individual response to treatment. However, PRN range opioid orders have recently come under scrutiny as a source of confusion and as a medication management safety issue. How nurses administer range orders may vary based on their interpretation of the intent of an order, inadequate knowledge of analgesic titration, or exaggerated concerns about opioid safety. The purpose of this study was to investigate nurses' opinions of the appropriate implementation of range orders. Six hundred two nurses from one large academic medical center and one multihospital system completed an online survey using theoretic clinical vignettes to examine their opinions of appropriate analgesic administration practices. The majority of participants chose appropriate responses to the vignettes; however, there was a great deal of variability in responses. Those who had attended pain management courses were more likely to have a higher percentage of appropriate responses than those who had not attended courses. Years in practice and educational level were not significantly related to percentage of appropriate responses; however, there was a trend for nurses with a master's degree to have a higher percentage than nurses with other educational preparation. Consideration of opioid pharmacokinetics can provide logic to develop a new paradigm where range orders are replaced with orders that provide more explicit instructions to titrate an opioid to the most effective dose.     

Dynamic fluorescence imaging of indocyanine green for reliable and sensitive diagnosis of peripheral vascular insufficiency

Quantitative measurement of functional tissue perfusion is essential for early diagnosis and proper treatment of peripheral arterial occlusive disease (PAOD). We have previously demonstrated that dynamic imaging of near-infrared fluorophore indocyanine green (ICG) can be a noninvasive and sensitive tool to measure tissue perfusion. In the present study, we investigated the clinical efficacy of ICG perfusion imaging method for the diagnosis of PAOD. Total nineteen PAOD patients and age-matched controls (n = 10) were evaluated for lower extremity tissue perfusion using ICG perfusion imaging. The perfusion rates of the lower extremities with severe PAOD (n = 25 legs, 16.6 ± 8.3%/min) were significantly lower than those of normal controls (38.1 ± 17.3%/min, p < 0.001). In cases of mild PAOD, the perfusion rates (n = 11 legs, 18.3 ± 10.3%/min) were also significantly lower compared to the control; while the conventional ankle-brachial index (ABI) test failed to detect mild functional impairment. These results collectively indicate that ICG perfusion imaging can be a very effective tool for diagnosis of PAOD with a superior efficacy in comparison to conventional ABI test.     

Stressors That Negatively Affect the Health of Radiology Professionals

Stress is one of the leading causes of mental and physical health problems in our society. This subject is nothing new to radiology professionals because of the constant exposure to various stressors. These stressors include staffing shortages, physical injuries, hospital violence, and diverse types of fatigue. Stressors are unique and personal to each individual, but they can also be applied to all radiology professionals and can correlate with health deficiencies. This paper examines research available on stress, and what stressors continuously affect the health of working professionals. To eliminate the negative effects of stressors, it is imperative for all health care providers to evaluate the bounds and risks to devise the most appropriate solution.