Severe Polyethylene Glycol Allergy Considerations for Perioperative Management: A Case Report.

Patients with severe polyethylene glycol (PEG) allergies face broad challenges, especially when presenting to the hospital for surgery, as PEG is used often as an excipient in medications and in medical supplies. Although rare, this allergy is increasingly reported and likely underdiagnosed. We present a patient with known past anaphylactic reaction to PEG and a detailed account of her perioperative course. More broadly, we provide recommendations and resources for the safe management of similar patients with a severe PEG allergy.

Maternal Human Immunodeficiency Virus (HIV) Drug Resistance Is Associated With Vertical Transmission and Is Prevalent in Infected Infants.

BACKGROUND: We aimed to assess if maternal human immunodeficiency virus (HIV) drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. METHODS: This was a case-control study of PROMISE study participants. "Cases" were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and "controls" were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers' and their infants' plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including antiretroviral therapy (ART) initiation and last study visits. RESULTS: Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero/peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. CONCLUSIONS: Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone.

OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories.

BACKGROUND: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. FINDINGS: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ±â€¯0.3% specificity and 98.2 ±â€¯0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ±â€¯0.6% specificity and 86.2 ±â€¯2.5% sensitivity, with 2.6 ±â€¯0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35-72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 ±â€¯0.8% accuracy. INTERPRETATION: OLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy. FUND: USA National Institutes of Health R01; the Clinical and Retrovirology Research Core and the Molecular Profiling and Computational Biology Core of the UW CFAR; Seattle Children's Research Institute; UW Holloman Innovation Challenge Award; Pilcher Faculty Fellowship.

Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.

Membrane-type I matrix metalloproteinases (MT1-MMP) is an enzyme critical to the remodeling and homeostasis of extracellular matrix, and when over expressed it contributes to metastasis and cancer cell progression. Because of its role and implication as a biomarker that is upregulated in various cancers, MT1-MMP has become an attractive target for drug discovery. A small pilot library of peptidomimetics containing a phosphoramidate core as a zinc-binding group was synthesized and tested for inhibitory potency against MT1-MMP. From this library, a novel two residue peptidomimetic scaffold was identified that confers potency against MT1-MMP at submicromolar concentrations. The results of this study confirm that for this scaffold, valine is favored as a P1 residue and leucine in the P1' position. Furthermore, steric tolerance was observed for the N-terminus, thus implicating that a second-generation library could be constructed to extend the scaffold to P2 without concomitant loss of affinity within the MT1-MMP catalytic domain.

The standardized and mini versions of the PAQLQ are valid, reliable, and responsive measurement tools.

OBJECTIVE: The Paediatric Asthma Quality of Life Questionnaire (PAQLQ) is a validated tool developed to assess the impact of symptoms on quality of life. Here we assess the validity, reliability and responsiveness of two new simpler versions of this questionnaire: the Standardised PAQLQ and the MiniPAQLQ. STUDY DESIGN AND SETTING: Participants included 42 children with asthma, who completed the PAQLQ, PAQLQ(S), MiniPAQLQ, Asthma Control Questionnaire, and Health Utilities Index at baseline, one, five and nine weeks. Concordance between questionnaires was examined using intraclass correlation coefficients (ICC), bias by paired Student's t-tests and closeness of association by Pearson correlation coefficients. RESULTS: Correlation coefficients for each of the corresponding domains of the PAQLQ with the PAQLQ(S) were strong (r>0.97), and moderate to strong (r=0.50-0.94) with the MiniPAQLQ. Reliability was strong for both the PAQLQ(S) (ICC>0.89) and MiniPAQLQ (ICC>0.91). The responsiveness index values for the PAQLQ(S) (0.96) and the MiniPAQLQ (1.05) were both higher than that of the original PAQLQ (0.90). Cross sectional and longitudinal correlation coefficients were similar for all three instruments. CONCLUSION: The PAQLQ(S) and the MiniPAQLQ are valid, reliable and responsive to change. They can be used with confidence for long-term monitoring in clinical trials.

Allergies in children.

An estimated 25% of the British population suffers from some form of allergic condition. Atopic dermatitis and food sensitivities are more common in infants and younger children, with hay fever (seasonal allergic rhinitis), perennial allergic rhinitis and allergic asthma developing throughout adolescence. Allergic reactions occur as a result of an interaction between allergen and mast cells via the antibody immunoglobulin E (IgE). Classic symptoms include itching, redness and swelling. These symptoms, and their time course, help the health professional to differentiate between allergic and non-allergic symptoms. Avoidance plays a part in management. Anaphylaxis is a medical emergency and recent guidelines recommend early use of epinephrine in patient with a severe allergic-type reaction.

"Why does he wheeze?": wheezing and asthma in young children.

Wheezing is common in young children and parents often worry that the child has asthma. The diagnosis of asthma in the under-fives is not always easy but assessing the severity of wheezing and whether it is transient, intermittent, persistent or associated with viral infection helps health professionals to rationalise treatment. This article outlines the different patterns of wheezing and some current approaches to management. Although wheezing and asthma are often associated, wheezing is commonly due to viral infection and more than 60% of children who wheeze during the first three years of life have ceased to do so by six years old. Parents of young children with wheeze and/or asthma need support and consistent advice from health professionals. Parents who smoke should be encouraged and helped to stop, as exposure to tobacco smoke increases the risk of a child developing recurrent wheeze, cough and breathlessness.