Initial apixaban dosing in patients with atrial fibrillation

Background

Apixaban is a non–vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function.

Hypothesis

The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction.

Methods

Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing‐relevant secondary diagnoses and co‐medication.

Results

We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664–0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076–1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881–0.940, P < 0.0001) were independent predictors for apixaban underdosage.

Conclusions

In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction.     

Recurrence of epidermoid cyst in the third ventricle. Case report

The authors present the case of a 34-year-old man. The patients was admitted for the second time in the clinic. A year before an epidermoid cyst of the third ventricle, obstructing the two foramen Monroe and causing acute hydrocephaly, was surgically removed. In the operative intervention a cerebral fenestration of the lateral cerebral ventricle was performed and the epidermoid cyst was totally extirpated through the right foramen Monroe under operative microscope. The patient was discharged in excellent state, without complaints and neurological symptoms. The patient received attacks of severe headaches, staggering gate and double vision two months before his second admission. The neurological examination revealed paresis of left nervus abducens, staggering gait and pronounced psychic symptoms. The computed tomography of the brain revealed cystic formation, 3.4 cm in diameter, in the front part of the third cerebral ventricle. The intervention was performed after preoperative management of the patient and a cystic tumor with the histologic characteristics of an epidermoid cyst was totally extirpated under operative microscope, using the same approach as in the first operation. The patient was discharged in good state without complaints and no abnormalities detected in the neurological status.     

Predictive value of teller Acuity Card Test (TACT) and comparison of recognition and grating acuities in premature children with and without residua of Retinopathy of Prematurity (ROP)

BACKGROUND: The aim of the study was to evaluate the predictive value of grating acuity as measured by the TAC Test (TACT) at the age of 6 months corrected age and to compare grating and recognition acuities in eyes with and without ROP residua at an age of three to seven years. PATIENTS AND METHODS: The development of visual acuity between 6 months and 3 - 7 years (4.5 years median) was evaluated in 87 eyes of 44 premature children born between the 24 th and 36 th week of gestation, with a birthweight ranging from 550 to 2580 g. Thirteen eyes reached threshold: ROP disease and underwent cryocoagulation. Grating acuity was measured with the TACT at 6 months corrected age and every half year up to three to seven years (median 4.5 years). Recognition acuity was measured with the Sheridan-Gardiner Test (SGT) at 4.5 years (median). TACT-results at 6 months corrected age and 3 - 7 years were compared for the group of patients with normal posterior pole and patients with ROP residua. Furthermore, SGT scores and TACT scores were compared at the 4.5 years follow-up. A visual acuity of >/= 0.1 (3 cy/ degrees ) and >/= 0.4 (13 cy/ degrees ) was considered favourable at the age of 6 months corrected age and 3 - 7 years, respectively. RESULTS: The TACT scores ranged from < 0.03 to 0.2 (< 1.0 to 6.5 cy/ degrees ) at 6 months and from < 0.05 to 2.0 (< 1.6 to 57 cy/ degrees ) at 3 - 7 years. In 77 % of cases the TACT scores at 6 months had predictive value for the further TACT scores and in 78 % for the optotype acuity. There was no difference between eyes with normal posterior pole and eyes with ROP residua concerning the predictive value of non favourable optotype acuity. CONCLUSIONS: Testing grating acuity at 6 months corrected age allows to roughly predict both grating and recognition acuities at the age of 3 - 7 years. No difference between patients with normal posterior pole and patients with ROP residua was found.     

In renal transplantation blood cyclosporine levels soon after surgery act as a major determinant of rejection: insights from the MY.S.S. trial

BACKGROUND: Target organs express antigens recognized directly by antigen-specific T cells, and their recognition is crucial to precipitate rejection. Then, the earliest T-cell activation is inhibited by cyclosporine A (CsA), the lowest would be the risk of rejection. Here, we aimed to assess this possibility in a large cohort of de novo kidney transplant recipients participating in an ongoing clinical trial, the Mycophenolate Steroid-Sparing (MY.S.S.) Trial. METHODS: Three-hundred-thirty-four patients entered the prospective, multicenter MY.S.S. trial. The main aim of the study was to assess the predictive value of serial evaluation of blood CsA trough concentration (C0) and 2-hour postdose drug (C2) levels alone or in combination, and to identify which is the critical posttransplant measurement to target CsA therapy in order to minimize the risk of acute rejection. A very large number of CsA trough (N= 2236) and C2 (N= 2128) measurements during the first 6 months postsurgery were available for analysis. Patients with delayed graft function were excluded. RESULTS: CsA trough levels measured at day 2 posttransplant were the strongest predictor of acute graft rejection over 6-month follow-up. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while for levels lower than 300 ng/mL, the risk of acute rejection was more than doubled. Higher levels failed to provide any further protection from graft rejection. CsA trough values predicted allograft rejection with an accuracy of 74%, while C2 levels considered alone had no predictive values at all. CONCLUSION: Findings that among serial daily measurements posttransplant those taken as early as at day 2 have by far the highest capacity to predict rejection episodes, underline the need of targeting CsA therapy very early posttransplant with the goal to modulate early enough T-cell activation at the interface between the recipient's blood and the graft where alloimmune response actually initiates.     

Nm23 gene product expression in invasive breast cancer--immunohistochemical analysis and clinicopathological correlation

The nm23 gene/protein is a putative metastatic suppressor identified a decade ago in a melanoma cell line. A number of laboratory, clinical and pathological studies have been carried out to define its real biological and biochemical function as a step in a complex metastatic process. In our study we examined the significance of nm23 expression in 164 breast cancer patients, aged 35 to 74 years, in comparison to other parameters such as age, menopausal status, histological grade, tumor size, lymph node status, and hormone receptor status. Overall survival (OS) and disease-free survival (DFS) were analyzed. The median follow-up was 84 months. Significant changes in OS were found for tumor size, nodal involvement and histological grade but there was no convincing correlation with nm23 expression. When patients were stratified according to nm23 expression, it was shown that overall survival in nm23 -positive patients was no longer than that in nm23 negative patients. It was also shown that patients who were lymph node negative and older than 50 years had longer OS than nm23 -negative patients. A statistical analysis shows that there is a correlation between axillary node status and nm23 expression (p = 0.018) as well as between patients' ages and nm23 expression (p = 0.043). There was no statistically significant correlation between nm23 expression, lymph node status and their combination on DFS.     

The use of acute normovolemic hemodilution in patients undergoing cardiac surgery

Avoiding allogeneic blood transfusion during cardiac surgery and during the post-operative period is of great importance. Acute normovolemic hemodilution (ANH) is one of the options for blood salvage. We have prospectively analyzed 310 consecutive patients (pts) after different open heart procedures, operated on during April-May, 2000. ANH was possible in 226 pts (73%) with hemoglobin level over 125 g/l and hematocrit over 36%. Of those, one unit of blood was withdrawn in 128 pts (70%), while two to five units of blood were taken in 68 pts (30%). Total number of autologous blood units taken was 296, for the average of 1.31 units/pt. Predictors of increased intra- and post-operative blood loss were hematocrit (Hct) <39% (76% vs. 24%, p<0.001), age over 65 (p=0.028), female sex (p=0.006), CPB duration over 90 min (63% vs. 37%; p<0.001) and preoperative left ventricular ejection fraction (LVEF) <35% (63% vs. 37%; p<0.001). All pts with the above-mentioned characteristics were in need for allogeneic blood transfusion. During their hospital stay, 142 pts did not get allogeneic blood (142/310, 46%), and all were in the ANH group (142/226, 62%).