Stability of Reconstituted Telavancin Drug Product in Frozen Intravenous Bags

Background and Objective:

Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at -20°C (-4°F) without light.

Methods:

Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method.

Results:

Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at -20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period.

Conclusion:

Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at -20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F -46°F]), and for 12 hours at room temperature when diluted into IV bags containing D5W, NS, or lactated Ringer’s solution.     

Predictors of HIV Among 1 Million Clients in High-Risk Male Populations in Tanzania

AIDS and Behavior - The World Health Organization identified men as an essential group to target with HIV testing and treatment strategies;: men who have sex with men (MSM) and male clients of...     

Amifostine does not prevent activation of TGFbeta1 but induces smad 7 activation in megakaryocytes irradiated in vivo

Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo.     

The association between sleep spindles and IQ in healthy school-age children

Recent studies have suggested that sleep is associated with IQ measures in children, but the underlying mechanism remains unknown. An association between sleep spindles and IQ has been found in adults, but only two previous studies have explored this topic in children. The goal of this study was to examine whether sleep spindle frequency, amplitude, duration and/or density were associated with performance on the perceptual reasoning, verbal comprehension, working memory, and processing speed subscales of the Wechsler Intelligence Scale for Children-IV (WISC-IV). We recruited 29 typically developing children 7–11 years of age. We used portable polysomnography to document sleep architecture in the natural home environment and evaluated IQ. We found that lower sleep spindle frequency was associated with better performance on the perceptual reasoning and working memory WISC-IV scales, but that sleep spindle amplitude, duration and density were not associated with performance on the IQ test.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

How well are DSM-5 diagnostic criteria for ASD represented in standardized diagnostic instruments?

Five years after the publication of DSM-5 in 2013, three widely used diagnostic instruments have published algorithms designed to represent its (sub-)criteria for Autism Spectrum Disorder (ASD) in children and adolescents. This study aimed to: (1) establish the content validity of these three DSM-5-adapted algorithms, and (2) identify problems with the operationalization of DSM-5 diagnostic criteria in measurable and observable behaviors. Algorithm items of the Autism Diagnostic Observation Schedule—Second Edition (ADOS-2), Developmental, Dimensional and Diagnostic Interview (3di) and Diagnostic Interview for Social and Communication Disorders—11th edition (DISCO-11) were mapped onto DSM-5 sub-criteria. The development and decision-making rules integrated in their algorithms were then compared with DSM-5. Results demonstrated significant variability in the number and nature of sub-criteria covered by the ADOS-2, 3di and DISCO-11. In addition to differences in the development of algorithms and cut-off scores, instruments also differed in the extent to which they follow DSM-5 decision-making rules for diagnostic classification. We conclude that such differences in interpretation of DSM-5 criteria provide a challenge for symptom operationalization which will be most effectively overcome by consensus, testing and reformulation.