Elevated Carbohydrate Antigen 19-9 in Patients with True (Epithelial) Splenic Cysts – Rare or Undiscovered?

Carbohydrate antigen 19-9 is a well known marker for pancreatic adenocarcinoma. However, its limitation is its nonspecificity, because elevated levels may be encountered in other gastrointestinal disorders, both benign and malignant. The following case is a patient with a true (epithelial) splenic cyst with elevated serum levels of carbohydrate antigen 19-9

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m$^{-}$$^{2}$ once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Elevated Carbohydrate Antigen 19-9 in Patients with True (Epithelial) Splenic Cysts – Rare or Undiscovered?

Carbohydrate antigen 19-9 is a well known marker for pancreatic adenocarcinoma. However, its limitation is its nonspecificity, because elevated levels may be encountered in other gastrointestinal disorders, both benign and malignant. The following case is a patient with a true (epithelial) splenic cyst with elevated serum levels of carbohydrate antigen 19-9

Pharmacist Remote Review of Medication Prescriptions for Appropriateness in Pediatric Intensive Care Unit

Background: One aspect of ordering and prescribing medication is the requirement for a trained professional to review medication orders or prescriptions for appropriateness. In practice, this review process is usually performed by a clinical pharmacist. However, in many medical centers there is a shortage of staff and a pharmacist is not always available.Objective: To determine whether remote review of medication orders by a pharmacist is a plausible method in a pediatric intensive care unit (PICU). Methods: A pharmacist from the pharmacy department reviewed medication orders of patients admitted to our PICU over a 7-month period for appropriateness. A special form for medical orders was filled in and sent to the physician in the PICU, who replied informing whether the recommendation had been accepted. The time spent by the pharmacist for this activity was recorded.Results: The review time for one medical record was 8.9 (95% CI, 6.9-10.9) minutes. Every additional drug prescribed increased the total review time by 0.8 (95% CI, 0.45-1.11) minutes. The pharmacist filled in 186 forms on 117 admissions for 109 children. The median review time was 15 (12.8-18.8) and 12 (9-15) minutes, respectively, for patients with psychiatric-neurologic disorders compared to those without (p=0.032). Usually, a daily workload of 240 minutes was needed for the pharmacist accompanying the round in contrast to 108 minutes per day needed to review all the medical records in 95% of the cases. The physician accepted 51.2%, rejected 11.9% and made no comment on 36.9% of the recommendations. Conclusion: Hospitals facing budget shortages can carry out focused remote reviews of prescriptions by the pharmacist

Unlicensed and Off-Label Medication Use in Pediatric and Neonatal Intensive Care Units: No Change over a Decade

<p><b>Article full text</b></p><p><br></p><p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-018-0732-y">https://link.springer.com/article/10.1007/s12325-018-0732-y</a></p><p></p><p><br></p><p><b>Provide enhanced content for this article</b></p><p><br></p><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p><p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p><br></p><p>Other enhanced features include, but are not limited to:</p><p><br></p><p>• Slide decks</p><p>• Videos and animations</p><p>• Audio abstracts</p><p> </p><p>• Audio slides</p> <p><b> </b></p

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls

Background: Late preterm (340&ndash;366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born &lt; 300 GA), and to term healthy control (TC) (&gt;370 week GA). Methods: Late preterm and early preterm (7&ndash;10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 &plusmn; 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP&minus;]) and to 25 TC children. Peak oxygen uptake (peakV&#775;O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 &plusmn; 15.1%, TC 112.4 &plusmn; 16.9%, p &lt; 0.001; EP+ 97.3 &plusmn; 25.5%, EP&minus; 85.4 &plusmn; 20.8%, p = 0.016 and p &lt; 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 &plusmn; 14.9% predicted, compared with 12.5 &plusmn; 87.8 in EP&minus;, 87.5 &plusmn; 16.9 in LP and 91.0 &plusmn; 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV&#775;O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV&#775;O2, were within the normal range, and no significant physiological exercise limitations were found

Exercise capacity in patients with cystic fibrosis vs. non-cystic fibrosis bronchiectasis.

BackgroundBronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients.MethodsCross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2).ConclusionsCPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis.Trial registrationClinicalTrials.gov, registration number: NCT03147651