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1.  Randomized Trial of Brinzolamide/Brimonidine Versus Brinzolamide Plus Brimonidine for Open-Angle Glaucoma or Ocular Hypertension 
Advances in Therapy  2014;31:1213-1227.
Introduction
Fixed-combination intraocular pressure (IOP)—lowering medications simplify treatment regimens for patients requiring 2 ocular hypotensive agents to maintain sufficiently low IOP. The aim of this study was to evaluate the safety and efficacy of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) versus concomitant administration of brinzolamide 1% plus brimonidine 0.2% (BRINZ + BRIM) in patients with open-angle glaucoma or ocular hypertension.
Methods
This was a prospective, phase 3, multicenter, double-masked, 6-month trial. Patients who had insufficient IOP control with monotherapy or who were receiving 2 IOP-lowering medications were randomized 1:1 to receive twice-daily BBFC or BRINZ + BRIM. IOP was assessed at 9 a.m. and 11 a.m. during week 2, week 6, month 3, and month 6 visits. The primary efficacy endpoint was mean diurnal IOP change from baseline to month 3; noninferiority was concluded if the upper limit of the 95% CI of the between-group difference was <1.5 mmHg. Supportive endpoints included mean IOP, IOP change from baseline, and percentage of patients with IOP <18 mmHg. Adverse events were recorded.
Results
The mean diurnal IOP change from baseline with BBFC (least squares mean ± standard error −8.5 ± 0.16 mmHg) was noninferior to that with BRINZ + BRIM (–8.3 ± 0.16 mmHg; mean difference −0.1 mmHg; 95% CI −0.5 to 0.2 mmHg). The upper limits of the 95% CIs were <1.5 mmHg at all time points. Decreases from baseline >8 mmHg were observed for least squares mean diurnal IOP in both groups as early as week 2 and continued to the end of the study. The results of all other supportive endpoints were similar to the primary efficacy endpoint. The most common ocular adverse drug reactions were hyperemia of the eye (reported as ocular or conjunctival hyperemia), visual disturbances, ocular allergic reactions, and ocular discomfort. Common systemic adverse drug reactions included dysgeusia, oral dryness, and fatigue/drowsiness.
Conclusion
Brinzolamide 1%/brimonidine 0.2% fixed combination was as well tolerated and effective as concomitant therapy with its components. BBFC reduces treatment burden in patients who require multiple IOP-lowering medications.
Electronic supplementary material
The online version of this article (doi:10.1007/s12325-014-0168-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s12325-014-0168-y
PMCID: PMC4271137  PMID: 25430900
Alpha-2 agonist; Carbonic anhydrase inhibitor; Concomitant; Fixed combination; Glaucoma; Intraocular pressure; Ocular hypertension; Ophthalmology; Simbrinza®
2.  Pneumoperitoneum as a result of a ruptured splenic abscess 
Journal of Surgical Case Reports  2013;2013(12):rjt111.
We encountered a case of ruptured splenic abscess presenting as peritonitis and pneumoperitoneum. Our patient did not have an underlying neoplasm nor was she immunosuppressed. In our case, splenectomy was the treatment of choice in combination with antibiotics, which proved to be a good outcome for the patient. Work-up for the cause of the abscess was negative, although bacteria predominately found in the oral flora were isolated from the abscess. We strongly encourage that splenic abscess be considered on the differential diagnosis of patients presenting with pneumoperitoneum and peritonitis, although a clinical rarity.
doi:10.1093/jscr/rjt111
PMCID: PMC3888002  PMID: 24968441
3.  Evaluation of nepafenac in prevention of macular edema following cataract surgery in patients with diabetic retinopathy 
Background
The purpose of this study was to evaluate nepafenac ophthalmic suspension 0.1% (Nevanac®; Alcon Research Ltd) in the prevention of macular edema following cataract surgery in diabetic retinopathy patients.
Methods
This was a multicenter, randomized, double-masked, vehicle-controlled study of 263 adult diabetic patients with nonproliferative diabetic retinopathy requiring cataract surgery. Patients were randomized (1:1) to instill nepafenac or vehicle three times daily beginning 1 day prior to surgery through day 90. Efficacy included the percentage of patients who developed macular edema (≥30% increase in central subfield macular thickness from baseline) and the percentage of patients with decreases of more than five letters in best-corrected visual acuity from day 7 to 90.
Results
A significantly lower percentage of patients in the nepafenac group developed macular edema relative to patients in the vehicle group (3.2% versus 16.7%; P < 0.001). A significantly lower percentage of patients in the nepafenac group had best-corrected visual acuity decreases of more than five letters relative to patients in the vehicle group on day 30 (P < 0.001), day 60 (P = 0.002), and day 90 (P = 0.006). The mean central subfield macular thickness and mean percent change from baseline in macular volume were also significantly lower in the nepafenac group versus the vehicle group at days 14 through 90 (P ≤ 0.005). No safety issues or trends were identified when dosing was increased to 90 days that negatively impacted the favorable benefit/risk profile of nepafenac.
Conclusion
Nepafenac demonstrated statistically significant and clinically relevant advantages compared with vehicle in preventing macular edema and maintaining visual acuity in diabetic patients following cataract surgery. These advantages were seen at multiple time points over the course of the 90-day therapy period. There was no clinically relevant increase in risk from 90 days dosing compared with 14 days. Therefore, with a similar safety profile and benefit in preventing macular edema and maintaining vision, the risk/benefit to the diabetic patient undergoing cataract surgery appears to be positive.
doi:10.2147/OPTH.S31902
PMCID: PMC3422154  PMID: 22927737
cataract extraction; diabetes; macular edema; nonsteroidal anti-inflammatory drug; topical; ocular surgery; retinopathy
4.  Detection of recurrent prostate cancer with 18F-fluorocholine PET/CT in relation to PSA level at the time of imaging 
Annals of Nuclear Medicine  2012;26(6):501-507.
Purpose
To evaluate fluorine-18 fluorocholine (FCH) PET/CT for the detection of recurrent prostate cancer in relation to prostate-specific antigen (PSA) level.
Methods
FCH PET/CT was performed in 50 patients with rising PSA levels at follow-up of primary treatment of prostate cancer (radical prostatectomy in 28, radiation therapy in 13, and brachytherapy in 9). PET detection rates were determined at various PSA thresholds and examined by receiver operating characteristic analysis.
Results
Findings consistent with recurrent prostate cancer were noted on FCH PET/CT in 31/50 (62 %) patients, with positive findings in 17/18 (94 %), and 11/13 (85 %), 2/7 (29 %), and 1/12 (8 %) patients with PSA >4, >2–4, >0.5–2, and ≤0.5 ng/mL, respectively. These findings were indicative of local/regional recurrence in 23 cases and systemic recurrence in 8 cases, with only a single route of recurrence (i.e., either hematogenous, lymphatic, or intraprostatic) in 84 % of PET scans with positive findings. Abnormal tumor activity was detected in 88 % of patients with a PSA level of 1.1 ng/mL or higher, and in only 6 % of patients with a PSA level below this threshold value.
Conclusion
FCH PET/CT may serve to identify the route of tumor progression in patients with recurrent prostate cancer; however, the likelihood of tumor detection may be related to the PSA level at the time of imaging.
doi:10.1007/s12149-012-0601-8
PMCID: PMC3400027  PMID: 22549847
Fluorocholine; Prostate cancer; Positron emission tomography
5.  Preventive Measures to Eliminate Asbestos-Related Diseases in Singapore 
Safety and Health at Work  2011;2(3):201-209.
The incidence of asbestos-related diseases (ARD) has increased in the last four decades. In view of the historical use of asbestos in Singapore since the country started banning it in phases in 1989 and the long latency of the disease, the incidence of ARD can be expected to increase further. As occupational exposure to asbestos still occurs, preventive measures to eliminate ARD continue to be required to protect the health of both workers and the public from asbestos exposure. The majority of occupational exposures to asbestos at present occur during the removal of old buildings. Preventive measures have been utilized by different government ministries and agencies in eliminating ARD in Singapore over the past 40 years. These measures have included the enforcement of legislation, substitution with safer materials, and engineering controls during asbestos removal as well as improvements in personal hygiene and the use of personal protective equipment. The existing Workman's Compensation System for ARD should be further refined, given that is currently stipulates that claims for asbestosis and malignant mesothelioma be made within 36 and 12 months after ceasing employment.
doi:10.5491/SHAW.2011.2.3.201
PMCID: PMC3430904  PMID: 22953203
Asbestos-related diseases; Prevention; Legislation; Compensation
6.  Acidification of the Oxygen Scavenging System in Single-Molecule Fluorescence Studies: In Situ Sensing with a Ratiometric Dual-Emission Probe 
Analytical Chemistry  2010;82(14):6132-6138.
For most of the single-molecule fluorescence studies to date, biomolecules of interest are labeled with small organic dyes which suffer from their limited photostability evidenced by blinking and photobleaching. An enzymatic oxygen scavenging system of glucose oxidase and catalase is widely used to improve the dye photostability but with the unfavorable side effect of producing gluconic acid. It is known that accumulation of this byproduct in solution can lead to considerable acidification, but the uncertainty in its severity under experimentally relevant conditions has been a long-standing area of concern due to the lack of a suitable assay. In this paper we report a fluorescence-based analytical assay for quantitatively assessing the acidification of oxygen scavenging systems in situ. By using a ratiometric, dual-emission dye, SNARF-1, we observed the presence and, for the first time, measured the severity of solution acidification due to the oxygen scavenging system for a number of conditions relevant to single-molecule studies. On the basis of the quantitative analysis of the acidification profile under these conditions, practical guidelines for optimizing the oxygen scavenging system are provided. This in situ assay should be applicable to a large variety of future single-molecule fluorescence studies.
doi:10.1021/ac1008749
PMCID: PMC2904532  PMID: 20583766

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