Is brimonidine ophthalmic a safe therapy for infants?

Brimonidine is a topical alpha-2 agonist commonly used in the treatment of glaucoma. Brimonidine toxicity resembles that of clonidine overdose and is probably due to both imidazoline and alpha-2 adrenergic receptor effects. We report a case of a 6-week-old infant with congenital glaucoma who developed bradycardia and hypotension following the administration of brimonidine 0.15% ophthalmic solution. There are occasional reports of brimonidine toxicity in the paediatric population but its overall safety profile in children<2 years of age remains uncertain. Brimonidine is not dosed by weight and therefore paediatric patients may be at increased risk for systemic toxicity. It is recommended that the use of this medication be carefully considered in children<2 years of age. Physicians should be aware of its side effect profile because of its general use in the paediatric population.     

Tap into NCLEX® success

This paper describes a triangulated approach for increasing National Council Licensure Examination (NCLEX®) pass rates. Readers will learn how to implement three powerful strategies to promote NCLEX® success.

• 1)Test: Quickly and effectively transform test items to the application or higher level.
• 2)Align: Evaluate curricula for alignment with NCLEX® standards. Align didactic and clinical teaching to prepare students for more challenging exams.
• 3)Prioritize: Make decisions about nice-to-know versus need-to-know content. Critically examine course requirements and assignments to verify student workload.

     

Improving the CellSearch® system

Introduction: The CellSearch® CTC test enumerates tumor cells present in 7.5 ml blood of cancer patients. improvements, extensions and different utilities of the cellsearch system are discussed in this paper.

Areas covered: This paper describes work performed with the CellSearch system, which go beyond the normal scope of the test. All results from searches with the search term ‘CellSearch’ from Web of Science and PubMed were categorized and discussed.

Expert commentary: The CellSearch Circulating Tumor Cell test captures and identifies tumor cells in blood that are associated with poor clinical outcome. How to best use CTC in clinical practice is being explored in many clinical trials. The ability to extract information from the CTC to guide therapy will expand the potential clinical utility of CTC.     

Evaluation of LOCI® technology-based thyroid blood tests on the Dimension Vista® analyzer

ObjectivesTo assess the performance of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) determinations by luminescent oxygen channeling immunoassay (LOCI®) technology on the Dimension Vista® analyzer (Siemens Healthcare Diagnostics).Design & methodsWe assessed 1) functional sensitivity for TSH (FSe-TSH), and intra- and inter-assay variations for TSH, FT4 and FT3 on Vista®; 2) comparisons of serum and heparin-treated plasma on Vista®; 3) comparisons of a) plasma TSH by Vista® versus electrochemiluminescence (ECLIA) on Roche Modular® analyzer, and b) plasma FT4 and FT3 by Vista® versus Immunotech®-Beckman radioimmunoassay (RIA); and 4) association of albumin and prealbumin levels with free thyroid hormone concentrations on Vista®.Results1) FSe-TSH concentration was below 0.005 mIU/L. Maximum intra-assay CVs (2.1%, 1.4%, 5.2%) and inter-assay CVs (16.5%, 5.1%, 5.8%) were good for TSH, FT4 and FT3 respectively. 2) Heparin-treated plasma samples consistently gave slightly higher values than serum for TSH, FT4 and FT3. 3) Passing–Bablok regression gave: TSH: [LOCI] = 0.91[ECLIA] ? 0.08 (concordance correlation coefficient ρ_c = 0.95); FT4: [LOCI] = 1.05[RIA] ? 1.55 (ρ_c = 0.80); and FT3: [LOCI] = 1.05[RIA] ? 0.06 (ρ_c = 0.81). 4) Both serum albumin and prealbumin concentrations were positively associated with FT3 levels and negatively associated with FT4 levels in patients.ConclusionLOCI® is accurate for TSH, FT4 and FT3 analysis. Despite a slight significant bias compared to ECLIA, LOCI® is precise for TSH and fulfills the third-generation criteria. However, the poor concordance between LOCI® and RIA for FT4 and FT3, and the dependence of these hormones on binding proteins require further investigation.     

ACR Appropriateness Criteria® Multiple gestations

Multiple gestations are high-risk compared with singleton pregnancies. Prematurity and intrauterine growth restrictions are the major sources of morbidity and mortality common to all twin gestations. Monochorionic twins are at a higher risk for twin-twin transfusion, fetal growth restriction, congenital anomalies, vasa previa, velamentous insertion of the umbilical cord and fetal death. Therefore, determination of multiple gestation, amnionicity and chorionicity in the first trimester is important. Follow up examinations to evaluate fetal well-being include assessment of fetal growth and amniotic fluid volume, umbilical artery Doppler, nonstress test and biophysical profile. To date, there is a paucity of literature regarding imaging schedules for follow-up. At the very least, antepartum testing in multiple gestations is recommended in all situations in which surveillance would ordinarily be performed in a singleton pregnancy.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed biennially by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging.     

Evaluation of the comfort of Alphagan® P compared with Alphagan® in irritated eyes

The tolerability of brimonidine tartrate 0.15%--referred to as bromonidine-Purite 0.15% in this study--was compared with brimonidine tartrate 0.2% in irritated eyes of healthy volunteers as well as patients with glaucoma or ocular hypertension (N=20) in a 2-week, single-center, randomized, double-masked, crossover study. Participants were evaluated at days 0, 7, 11, and 15. At day 0, they were exposed to a controlled adverse environment (CAE), in which humidity, temperature, and airflow was regulated, for up to 90 minutes. Participants who reported a sufficient level of bilateral ocular discomfort during exposure to the CAE were enrolled in this study and received 1 drop of brimonidine-Purite 0.15% in 1 eye and 1 drop of brimonidine tartrate 0.2% in the contralateral eye. Immediately following instillation, participants were asked to indicate their preference for either study medication. The study medications were not used between days 0 and 7. From day 7 to 10, participants administered either drug bilaterally. On day 11, the treatment was crossed over, and participants were asked to compare the preferred medication with their previous regimen. They continued to administer the drug bilaterally twice daily until day 15, when the preferred medication was again compared with the previous regimen. Following CAE exposure at visit 1, 70.6% of the participants preferred brimonidine-Purite 0.15% over brimonidine tartrate 0.2% and indicated that it was significantly more comfortable than brimonidine tartrate 0.2% (P=.009). When given brimonidine-Purite 0.15% first before switching to brimonidine tartrate 0.2%, 80% of participants preferred brimonidine-Purite 0.15% (P=.012). When given brimonidine tartrate 0.2% first before switching to brimonidine-Purite 0.15%, 85% preferred brimonidine-Purite 0.15% (P=.001). The results of this study suggest that brimonidine-Purite 0.15% is significantly more comfortable than brimonidine tartrate 0.2% in patients with irritated eyes.     

TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

Long-term stability of procalcitonin in frozen samples and comparison of Kryptor® and VIDAS® automated immunoassays

ObjectivesTo assess long-term stability of PCT in deep-frozen samples and assess whether Kryptor procalcitonin cutoff ranges can be transferred on the bioMérieux VIDAS system.Design and methodsSamples from two intervention studies (ProRESP and ProCAP) were retested on both systems and compared with Passing–Bablok regression, Bland–Altman difference plot, and analysis of concordance over 4 medically relevant cutoff ranges.ResultsProlonged storage resulted in a significant decline of median procalcitonin values of 11.4% and 13.5% in ProRESP and ProCAP cohorts. Regression analysis showed that both methods correlated well (r = 0.982, n = 304) but with a deviation from the line of identity (y = 1.234x ? 0.018). The Bland–Altman plot indicated an average relative bias of 17.1% (2 SD limits: ? 56.4% to 90.5%). Concordance over all 4 categories was 82.6%, without a significant difference in frequency distribution between methods.ConclusionAn only modest decline of measured PCT levels of around 10% after long-term deep-frozen storage was found. The VIDAS procalcitonin assay showed good correlation and concordance with the established Kryptor method. Both techniques can be used with the same nominal procalcitonin cutoff ranges in clinical routine.     

Metrazol® Treatment of the Geriatric Patient

The twin-study method has contributed greatly to our knowledge of the interrelationships of heredity and environment. Studies of monozygotic twins reared together and apart and studies of concordance for certain traits in monozygotic and in dizygotic twins are reviewed.     

ACR Appropriateness Criteria® non-spine bone metastases

Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. EBRT may be combined with other local therapies like surgery or with systemic treatments like chemotherapy, hormonal therapy, osteoclast inhibitors, or radiopharmaceuticals. EBRT is not commonly recommended for patients with asymptomatic bone metastases unless they are associated with a risk of pathologic fracture. For those who do receive EBRT, appropriate fractionation schemes include 30?Gy in 10 fractions, 24?Gy in 6 fractions, 20?Gy in 5 fractions, or a single 8?Gy fraction. Single fraction treatment maximizes convenience, while fractionated treatment courses are associated with a lower incidence of retreatment. The appropriate postoperative dose fractionation following surgical stabilization is uncertain. Reirradiation with EBRT may be safe and provide pain relief, though retreatment might create side effect risks which warrant its use as part of a clinical trial. All patients with bone metastases should be considered for concurrent management by a palliative care team, with patients whose life expectancy is less than six months appropriate for hospice evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.