An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan(®) RC Early Analysis Review (CLEAR) trial.

PURPOSE: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. SUBJECTS AND METHODS: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. RESULTS: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from -2.3%±17.3% to -26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. CONCLUSION: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%-15% reduction in IOP.

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial.

BACKGROUND: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. METHODS: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. RESULTS: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. CONCLUSION: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.

Documentation of daily sit-to-stands performed by community-dwelling adults.

No information exists about how many sit-to-stands (STSs) are performed daily by community-dwelling adults. We, therefore, examined the feasibility of using a tally counter to document daily STSs, documented the number of daily STSs performed, and determined if the number of STSs was influenced by demographic or health variables. Ninety-eight community-dwelling adults (19-84 years) agreed to participate. After providing demographic and health information, subjects used a tally counter to document the number of STSs performed daily for 7 consecutive days. All but two subjects judged their counter-documented STS number to be accurate. Excluding data from these and two other subjects, the mean number of STSs for subjects was 42.8 to 49.3, depending on the day. The number was significantly higher on weekdays than weekends. No demographic or health variable was significantly related to the number of STSs in univariate or multivariate analysis. In conclusion, this study suggests that a tally counter may be a practical aid to documenting STS activity. The STS repetitions recorded by the counter in this study provide an estimate of the number of STSs that community-dwelling adults perform daily.

What is the potential for overdiagnosis of heparin-induced thrombocytopenia?

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4//heparin (PF4/H) complexes. According to the "iceberg model," only a subset of anti-PF4/heparin antibodies of IgG class evincing strong platelet-activating properties cause clinical HIT. Since many centers rely predominantly on an anti-PF4/polyanion enzyme-immunoassay (EIA) to diagnose HIT, we estimated the potential for overdiagnosis when only this single test is available. We examined a database of 100 patients in whom the probability of HIT had been estimated using a clinical scoring system (4Ts), and where patients underwent systematic testing for HIT antibodies using three assays: the platelet serotonin release assay (SRA), an "in-house" EIA that detects IgG anti-PF4/heparin antibodies (EIA-IgG), and a commercial EIA that detects anti-PF4/polyanion antibodies of all three immunoglobulin classes (EIA-GTI). Whereas 16 of 100 patients fulfilled a "classic" definition of HIT (intermediate/high probability plus strong platelet-activating anti-PF4/heparin IgG antibodies), an additional 16 patients fulfilled a "liberal" definition in which any investigated patient (irrespective of the pretest probability) who had a positive EIA-GTI was considered to have HIT. The clinical features of these 16 additional patients--including generally weak antibodies and low risk for thrombosis--suggest underlying non-HIT explanations for thrombocytopenia. Patients with a positive SRA generally corresponded to those with intermediate or high pretest probability of HIT who also had strong EIA-GTI reactivity (>1.20 OD units). We conclude there is the potential to overdiagnose HIT by approximately 100% if any positive EIA is considered to "confirm" the diagnosis of HIT irrespective of the clinical scenario.

Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a "self" protein-platelet factor 4-bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.

Laboratory testing for the antibodies that cause heparin-induced thrombocytopenia: how much class do we need?

Heparin-induced thrombocytopenia (HIT) is usually caused by platelet-activating antibodies of immunoglobulin G class that recognize platelet factor-4 (PF4) bound to heparin or certain other polyanions. Commercial enzyme immunoassays (EIAs) for PF4/polyanion-reactive antibodies detect two immunoglobulin classes (IgA and IgM) besides IgG. To investigate whether the additional detection of these antibody classes improves or worsens assay operating characteristics, we compared the sensitivity and specificity of EIAs that detect these 3 immunoglobulin classes individually with that of a commercial EIA (Genetic Testing Institute, GTI), as well as a platelet-activation assay, the serotonin-release assay (SRA). We compared the operating characteristics of these 5 assays by evaluating 448 patients, in 14 of whom clinical HIT developed, who received either unfractionated or low molecular weight heparin in prospective studies that included systematic platelet-count monitoring and serologic evaluation for anti-PF4/polyanion antibodies. We found that the SRA and IgG and commercial EIAs had similar high sensitivity for HIT; however, diagnostic specificity (for unfractionated and low molecular weight heparin, respectively) varied considerably, as follows: SRA (95.1%, 97.2%) > IgG EIA (89.0%, 93.7%) > GTI EIA (74.2%, 87.6%). Additional detection of IgA and IgM antibodies by the GTI EIA worsened test specificity by detecting numerous nonpathogenic antibodies. Moreover, the frequency and magnitude of IgA and IgM antibody formation in non-HIT immune responses did not differ from that exhibited by patients in whom clinical HIT developed. We conclude that an EIA that detects anti-PF4/polyanion antibodies of only the IgG class has greater diagnostic usefulness in revealing clinical HIT than does an assay that also detects IgA and IgM class antibodies.

Evaluation of the effectiveness of two clinical training procedures to elicit yes/no responses from patients with a severe acquired brain injury: a randomized single-subject design.

PRIMARY OBJECTIVE: Thirteen (10 males) participants with severe acquired brain injuries (ABI) were randomly assigned to two treatments, A or B (ABAB, BABA) in a crossover study to determine which treatment approach elicited more consistent and reliable yes/no responses. RESEARCH DESIGN: Treatment A consisted of an enriched stimulus environment, collaborative multidisciplinary interventions and additional yes/no response training, while Treatment B consisted of the standard hospital environment and interventions. MAIN OUTCOMES: An ANOVA showed no order effect (AB vs BA; p=0.60), but a trend (A vs B;p=0.07) towards statistical significance for increased responsiveness with treatment A. Inter-raterreliability (n=10) ranged from fair-to-good, intra class correlation (ICC) 0.51; 95% confidence interval (CI) (0.29-0.93). Post-hoc analyses showed statistically significant increased responsiveness for four participants with treatment A (p<0.001). CONCLUSION: Evidence is provided that enhanced communication strategies can improve responsiveness in a sub-group of participants with severe acquired brain injuries.

Central venous catheters and upper-extremity deep-vein thrombosis complicating immune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a transient antibody-mediated hypercoagulability state strongly associated with lower-limb deep-vein thrombosis (DVT). Whether HIT is additionally associated with upper-limb DVT--either with or without central venous catheter (CVC) use--is unknown. We therefore studied 260 patients with antibody-positive HIT to determine the influence of CVC use on frequency and localization of upper-extremity DVT in comparison with 2 non-HIT control populations (postoperative orthopedic surgery and intensive-care unit patients). Compared with the control populations, both upper- and lower-extremity DVTs were found to be associated with HIT. Upper-extremity DVTs occurred more frequently in HIT patients with a CVC (14 of 145 [9.7%]) versus none of 115 (0%) patients without a CVC (P =.000 35). All upper-extremity DVTs occurred at the CVC site (right, 12; left, 2; kappa = 1.0; P =.011). We conclude that a localizing vascular injury (CVC use) and a systemic hypercoagulability disorder (HIT) interact to explain upper-extremity DVT complicating HIT.