Central Nervous System-related Events Research Articles

Granulocyte Colony-Stimulating Factor Is Safe and Well Tolerated following Allogeneic Transplantation in Patients with Sickle Cell Disease

Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD), because life-threatening complications can ensue in the presence of sickle vasculopathy. The safety profile of G-CSF after HSCT for SCD has not been described, however. We report clinical outcomes in the first 100 days post-HSCT in 62 patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced- intensity conditioning HSCT for SCD. The patients received G-CSF for a median of 9 days (range, 5 to 33 days) post-transplantation from the best available stem cell source. Preparation for transplantation included a target hemoglobin S level of ≤45%. Neutrophil engraftment (absolute neutrophil count >0.5×103/mL) was achieved at a median of 13 days (range, 10 to 34 days), and platelet engraftment (>50×103/mL) was achieved at a median of 19 days (range, 12 to 71 days). The median duration of inpatient hospitalization following stem cell infusion (day 0) was 21.5 days (range, 11 to 33 days). No patient developed SCD-related complications following G-CSF use. The most common organ toxicities encountered between G-CSF initiation (on day +7) and day +100 were anorexia (n=14), hypertension (n=11), and electrolyte imbalance requiring correction (n=9). Central nervous system-related events were noted in 5 patients, all of whom had preexisting cerebral vasculopathy/moyamoya disease, attributed to reversible posterior leukoencephalopathy syndrome in the presence of calcineurin inhibitor therapy and hypertension. We conclude that G-CSF does not adversely impact SCD HSCT recipients and can be safely used post-transplantation to enhance neutrophil recovery.

Impact of Etanercept Therapy on Disease Activity and Health-Related Quality of Life in Moderate Rheumatoid Arthritis Patients Population from a National British Observational Cohort

ObjectivesTo describe a population with moderate rheumatoid arthritis (RA) before biologic initiation and assess change in disease status, health-related quality of life (HRQOL), and adverse events in etanercept (ETN)-treated patients. MethodsData on adult patients with moderate RA (3.2 < Disease Activity Score in 28 Joints [DAS28] ≤ 5.1) were retrospectively analyzed from the British Society for Rheumatology Biologics Register comparing a nonbiologic-treated group (nBG) using at least one traditional disease-modifying antirheumatic drug to a biologic group (BG) treated with ETN. The HRQOL was assessed by using the Health Assessment Questionnaire disability index score. To mitigate confounding, we controlled for drivers of progression. Appropriate univariate, multivariate, and regression analyses were used. ResultsA total of 1754 patients with RA were assessed (211 BG and 1543 nBG). Compared with the nBG, the BG tended toward higher disease activity, such as significantly higher tender joints and DAS28. The BG compared with the nBG had 1) a greater reduction in DAS28 and Health Assessment Questionnaire scores; 2) disease remission occurring more often (odds ratio = 2.7; P = 0.006); and 3) progression occurring in fewer patients (odds ratio = 0.3; P = 0.002). BG patients had a higher incidence of “other serious infection” and “other central nervous system–related events,” with no significant differences in associated hospitalization rates or deaths. ConclusionsAmong patients with moderate RA from a clinical practice registry, ETN-treated patients had significantly higher disease activity at the time of biologic initiation but significantly reduced disease activity and better HRQOL after 6 months compared with nBG patients, although the possibility of unmeasured confounding remains. The ETN group reported significantly higher incidences of “other serious infections” and “other central nervous system–related events” without higher hospitalization rates.

Retrospective analysis of the safety profile of oral and intravenous ciprofloxacin in a geriatric population

Background: Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used in the treatment of a wide range of mild to moderate gram-positive and gram-negative infections. Although extensive information is available on the safety profile of ciprofloxacin in adults, few published data exist regarding the tolerability and toxicity of this drug in patients aged ≥65 years. Objectives: The objectives of this retrospective analysis were to compare the safety profile of ciprofloxacin in patients aged ≥65 years versus patients aged <65 years and to compare the adverse-event profile of ciprofloxacin with that of other comparator antimicrobial agents used in clinical trials. Methods: We retrospectively reviewed 23 prospective, controlled anti-infective clinical trials in the US Bayer ciprofloxacin database that included patients aged ≥65 years. These trials comprised the submission file of the original and supplemental New Drug Application for ciprofloxacin. The incidence of treatment-emergent and drug-related adverse events was assessed. Results: Of the 6863 patients in these 23 clinical trials, 3579 recieved ciprofloxacin therapy and 3284 received comparator antimicrobial agents. Of the ciprofloxacin-treated patients, 898 (25.1%) were aged ≥65 years; 887 (27.0%) of the patients who received comparator antimicrobial agents were aged ≥65 years. Among ciprofloxacin-treated patients, drug-related adverse events were reported more often in those aged <65 years (24.0%) compared with those aged ≥65 years (17.9%). The incidence of drug-related adverse events in the comparator group was also higher in those aged <65 years (25.1%) than in those aged >-65 years (16.8%). Premature discontinuation due to any adverse events was reported in 3.9% (105 or 2681) and 3.7% (33 of 898) of ciprofloxacin-treated patients aged <65 years and ≥65 years, respectively. Corresponding rates for the comparator antimicrobial group were 3.9% (93 to 2397) and 3.8% (34 of 887), respectively, for patients aged <-65 years and ≥65 years. The most common drug-related adverse events reported for ciprofloxacin-treated patients aged <65 years and >-65 years were digestive system-related (18.1% and 11.4%, respectively) and central nervous system-related events (6.6% and 4.9%, respectively). Conclusions: The retrospective analysis suggests that there is no clinically important difference in the safety profile of ciprofloxacin in patients aged >-65 years versus patients aged <65 years.