In Vitro Assessment for Dose Preparation and Simulated Administration of Azithromycin Suspensions via Enteral Feeding Tubes.

Administration of medication via enteral feeding tubes (EFT) is common in cases where patients are unable to swallow the dosage form or a patient is intubated. The SARS-CoV-2 (COVID-19, coronavirus disease 2019) epidemic created a need to rapidly evaluate potential treatment options to address the global pandemic including evaluation of azithromycin (AZM) as a mono or combination therapy. Due to the complicating medical conditions of COVID-19, in some cases patients may be unable to take medication orally and could require medication administration by alternate routes such as an EFT. The aim of this study was an in vitro assessment for the dose preparation and simulated administration of AZM suspensions, prepared from tablets and capsules, via nasogastric feeding tubes (NGT). AZM tablets and capsules were used to prepare aqueous suspensions from 250 to 2000 mg for administration via NGT. NGT between 8 and 12 French (Fr), from common materials of construction and typical lengths were evaluated. About 20 mL syringes were used with water as the diluent. The preparation and simulated NGT administration steps for AZM suspensions were evaluated in the laboratory studies and included assessment of in-use stability of the aqueous suspensions, chemical compatibility of prepared aqueous suspensions with the syringe and NGT, ease of delivery and accuracy of simulated administration. Analysis of the prepared sample solutions for assay/impurities was performed using chromatographic conditions based on the USP-NF monograph. Verification of dose preparation and simulated administration was performed for intact tablets, crushed tablets, and capsules. Aqueous suspensions prepared from intact tablets and capsules were exposed to dosing materials (enteral syringe and NGT) for a period of up to 4 hours at ambient conditions. Assessment of the ease of dose delivery and analyses of the resulting samples for assay, purity and total degradation products were performed. The laboratory studies verified a procedure to reliably prepare suspensions from AZM tablets and capsules, over a range of 250 to 2000 mg, that can be accurately administered through NGT in sizes of 8 to 12 Fr. No incompatibilities of the prepared aqueous AZM suspension with dosing materials were observed and acceptable stability was demonstrated for up to 4 hours.

Reducing unnecessary neonatal testing in infants of mothers with thyroid disease.

AIM: To examine the numbers of asymptomatic infants <8 weeks who had appropriate thyroid function tests (TFTs) in addition to the newborn screening test, because of maternal thyroid disease, before and after the implementation of an updated institutional guideline and staff education. METHODS: A medical record audit of infants <8 weeks born at a metropolitan teaching hospital, who had TFTs between 1 July 2017 and 31 October 2017 was performed as part of a quality improvement project. Records were reviewed to determine the indication for testing and whether this complied with the current 2011 institutional guideline. A multidisciplinary staff education package was developed to coincide with the publication of an updated guideline in August 2018. Staff education and resources were provided throughout July 2018. A post-intervention audit was repeated between 1 August 2018 and 1 December 2018, assessing compliance with the 2018 guideline. RESULTS: In the baseline period, 40 of 457 infants born had TFTs performed, of which 26 of 40 (65%) were for maternal thyroid disease. Of these 10 of 26 (38%) met the 2011 criteria for testing; 1 of 26 (4%) met the updated 2018 criteria. In the post-intervention period, 14 of 412 infants born had TFTs of which 5 of 14 (36%) were tested due to maternal thyroid disease and all were compliant with the new guideline. CONCLUSIONS: Baseline audit revealed unnecessary neonatal thyroid function testing of healthy babies. Implementation of an updated guideline and a brief, targeted education package successfully increased awareness of the updated recommendations, reduced unnecessary testing and led to improved practice.

Naturally occurring B-cell responses to breast cancer.

As demonstrated by the effectiveness of trastuzumab, antibodies against breast cancer antigens are a potentially potent mechanism of tumor control. While trastuzumab is administered exogenously, its efficacy suggests that induction of very high titer antibody responses in vivo might also be therapeutic. Both naturally occurring and vaccine-induced antibody responses to some breast cancer antigens are associated with improved survival in some cases. However, the improvement in survival associated with antibody responses to breast cancer is modest, and tumor regression is not known to be associated with the natural antitumor antibody response, indicating a need for improved understanding of the natural antitumor antibody response. Naturally occurring B-cell responses in the form of serum antibody, tumor reactive lymph node B cells, and tumor-infiltrating B cells have been described, and a variety of breast tumor-associated antigens have been identified based on reactivity of patient antibodies. This review discusses current knowledge of humoral immunity to breast cancer with regard to specific antigens and the basis for their immunogenicity, and the contexts (tumor, lymph node, serum) in which responses are observed. With few exceptions, "tumor-associated antigens" identified with naturally occurring antibodies may be overexpressed on tumor but are in fact nonspecific autoantigens. This suggests that while overexpression or aberrant processing can increase immunogenicity in some cases, the immunogenicity of many or even most tumor-associated antigens is a function of expression in tumor or the result of ancillary tumor factors.