Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study.

BACKGROUND: The purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME). METHODS: This was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant. RESULTS: One hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 µm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3-4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P<0.0001), followed by RVO (1.3±0.5, P<0.01) and DME (0.7±0.5, P>0.05). Significant decreases in CRT were observed: -255.6±43.6 µm for uveitis, -190.9±23.5 µm for DME, and -160.7±39.6 µm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s). CONCLUSION: DEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.

A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV(1)) than those patients who have stopped smoking. OBJECTIVES: To assess the effect of tiotropium on pre-dose (trough) FEV(1) in patients with COPD followed in Canada. METHODS: A total of 913 patients were randomly assigned to receive either tiotropium 18 mug once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV(1), FEV(6) and forced vital capacity), symptoms, health-related quality of life (St George's Respiratory Questionnaire) and exacerbations were examined. RESULTS: Tiotropium improved trough FEV(1) in both current and ex-smokers compared with placebo. Baseline FEV(1) in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14+/-0.04 L (P<0.001) in the smoker group and 0.08+/-0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV(6) compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George's Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005). CONCLUSIONS: Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.

The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Patients with acute myeloid leukemia are at risk of bleeding. The risk factors for different severities of bleeding are poorly studied. DESIGN AND METHODS: Data from Rebulla et al. were analyzed in an exploratory analysis using multivariate Cox regression analyses for time-to-first bleed with time-depend- ent covariates reflecting measures of clinical and laboratory variables on the previous day. The relationships of the variables with three bleeding categories were studied: mild bleeding (WHO grades 1 and 2) clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3 and 4). RESULTS: Bleeding of any severity occurred in 149 (58.4%) of 255 patients. There were 743 days of bleeding over 7335 patient-days of observation. Risk factors for mild bleeding included increased body temperature and decreased platelet count; the risk was decreased with administration of antifungal medication or platelet transfusion on the previous day. Risk factors for clinically significant bleeding included grade 1 bleeding on the previous day, decreased platelet count and elevated body temperature. Decreased platelet count and mild bleeding on the previous day were risk factors for severe bleeding. Higher hemoglobin values were associated with a delay in the time-to-first clinically significant bleed. INTERPRETATION AND CONCLUSIONS: These results support clinical guidelines for increasing the platelet transfusion threshold in the presence of fever and support the use of milder bleeding symptoms as an outcome in clinical trials. The suggestion that hemo- globin concentration maybe predictive of bleeding risk supports the hypothesis that this maybe a valuable intervention in anemic thrombocytopenic patients at high risk of bleeding.

Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.

BACKGROUND: Previous risk factor studies in cardiac transplant patients have analyzed pre-transplant risk factors as they relate to outcomes. This study is the first in-depth multicenter assessment of ongoing post-transplant risk factors in heart transplant patients and their impact on 5-year outcomes. METHODS: We reviewed 280 heart transplant patients who survived > 1 year for the impact of post-transplant risk factors (hyperlipidemia, hypertension, diabetes, body mass index [BMI] and renal dysfunction: 8 to 18 possible measurements over 5 years) on outcomes, including death, cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). RESULTS: Upon multivariate Cox regression analysis, significant findings were high total-cholesterol for NF-MACE (relative risk [RR] = 4.34, confidence interval [CI] 1.35 to 13.98, p = 0.01), presence of diabetes for NF-MACE (RR = 3.96, CI 1.24 to 12.65, p = 0.02) and high serum creatinine for graft death (RR = 1.59, CI 1.35 to 1.87, p < 0.001). No covariates were found to be significant for CAV. Other significant risk factors by univariate Cox regression models with time-dependent covariates included BMI > or = 33 for graft death. CONCLUSIONS: Post-transplant risk factors of hypercholesterolemia and diabetes are associated with NF-MACE, whereas high serum creatinine and BMI > or = 33 are associated with graft death. Risk factor modification, including direct therapy to minimize risk factors, should be considered.

A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia.

BACKGROUND: Recently, bleeding has been used in platelet (PLT) trials rather than surrogate outcomes. The purpose of this study was to provide a descriptive summary of data from PLT studies conducted in four countries and exploratory analyses to determine the relationship between bleeding and PLT count. STUDY DESIGN AND METHODS: A descriptive analysis was performed on original data from the Italian trigger study, the US TRAP study, the Canadian febrile reaction study, and a clinical chart review from one hospital site in the United Kingdom. The relationship between bleeding and PLT count was explored with the Italian data. RESULTS: A total of 897 patients with acute leukemia received 10,506 PLT transfusions. Grade 3 or Grade 4 WHO bleeding frequency was 28.1 percent (252/897) but varied by country: Italy, 10.8 percent (27/250); United States, 36.4 percent (217/598); Canada, 18.9 percent (7/37); and the United Kingdom, 8.3 percent (1/12). Grade 1 or Grade 2 bleeding was reported only in the Italian study (46.4%[116/250] and 11.6%[29/250], respectively). The relative rates of WHO Grade 2, 3, or 4 bleeding for PLT counts in the ranges of 0 to 4, 5 to 9, 10 to 14, and 15 to 19 (x10(9)/L) were 8.8, 1.9, 1.8, and 1.2, respectively, compared to those counts within the range of 20 to 29 (x10(9)/L). CONCLUSION: The study provides descriptive data on PLT use and frequency of bleeding. When PLT counts were 0x10(9) to 4x10(9) per L there was an eightfold increase in bleeding and a twofold risk increase when counts were 5x10(9) to 14x10(9) per L compared to the 20x10(9) to 29x10(9) per L reference range. The increased rate of bleeding at low counts occurred despite PLT therapy.