Medication Desensitization: Single Intravenous Bag Method, in 3 Pediatric Patients.

Chemotherapies and biologic agents are known to cause hypersensitivity reactions (HSRs). It is imperative that pediatric patients receive these agents to treat their cancer or other rare condition, as oftentimes there are no available therapeutic alternatives. Successful medication desensitization has been described previously with a 12-step method using 3 intravenous (IV) infusion bags of varying concentrations. However, this 12-step process is time and resource intensive and increases the risk for medication errors. A recent study successfully used a simplified 12-step method with a single IV infusion bag for a paclitaxel desensitization. From the results of this study, our institution used this single IV infusion bag method for desensitization with 3 different medications. Two of these experiences were successful. We share those 3 experiences in this report.

Extra-axial haemorrhages in young children with skull fractures: abuse or accident?

OBJECTIVE: Infant and toddler subdural haemorrhages (SDH) are often considered indicative of abuse or major trauma. However, accidental impact events, such as falls, cause contact extra-axial haemorrhages (EAHs). The current study sought to determine frequency and clinical behaviour of EAHs with infant and toddler accidental and abusive skull fractures. PATIENTS AND METHODS: Children aged <4 years with accidental skull fractures and abusive fractures identified by CT at two paediatric tertiary care centres. Clinical data were abstracted by child abuse paediatricians and images were reviewed by paediatric radiologists. Data were analysed using univariate and multivariate logistic regression as well as descriptive statistics. RESULTS: Among 227 subjects, 86 (37.9%) had EAHs. EAH was present in 73 (34.8%) accidental and 13 (76.5%) of the abusive injuries. Intracranial haemorrhage rates were not different for children with major or minor accidents but were fewer than abused. EAH was equally common with falls <4 and >4 ft. EAH depths did not differ by mechanism, but 69% of accidental EAHs were localised solely at fracture sites vs 38% abuse. Widespread and multifocal EAHs were more common with abuse. Children with abuse or major accidental injuries presented with lower initial Glasgow Coma Scales than those with minor accidents. Abused children had initial loss of consciousness more often than those with either minor or major accidents. CONCLUSIONS: Simple contact EAHs were common among children with minor and major accidental skull fractures. Accidental EAHs were more localised with less neurological dysfunction than abusive.

Variation in access to specialist services for neurosurgical procedures in adults with epilepsy in England, a cohort study.

PURPOSE: To understand if primary consultation at tertiary epilepsy centres (TEC) in England impacts access to neurosurgical procedures (resective surgery, vagus nerve stimulator [VNS], deep brain stimulator [DBS]). METHODS: Adults with epilepsy, and with a first neurology outpatient visit (index) between 01/01/2013 and 31/12/2015, were followed using English Hospital Episode Statistics from index date to 31/12/2019. Analyses were stratified by geographic location, learning disability record, and whether the index or follow-up visits were at a TEC. RESULTS: 84,093 people were included, with mean 5.5 years of follow-up. 12.4% of the cohort had learning disability (range 10.1%-17.4% across regions). TEC consultations varied by National Health Service regions and Clinical Commissioning Groups. 37.5% of people (11.2%-75.0% across regions) had their index visit at a TEC; and, of those not initially seen at a TEC, 10.6% (6.5%-17.7%) subsequently attended a tertiary centre. During follow-up, 11.1% people (9.5%-13.2%) visited a neurosurgery department, and 2.3% of those (0.9%-5.0%) then underwent a neurosurgical procedure, mainly VNS implantation. Median time from index date to first visit at a neurosurgery centre was 7 months (range 6-8 months across regions) and 40 months to procedure (36.5-49 months, 37.0 months in people with index visit at a TEC and 49.0 months otherwise). People with learning disability were less likely to have resective surgery (<0.5% versus 1.0% in those without) and more likely to undergo VNS implantation (5.8% versus 0.8%). CONCLUSION: Although clinically recommended for suitable individuals, neurosurgical procedures in epilepsy remain uncommon even after consultation at a TEC. Geographical variation in access to TECs was present.

Ultrafast relaxation dynamics of Au38(SC6H13)24 monolayer-protected clusters resolved by two-dimensional electronic spectroscopy.

Electronic relaxation dynamics of neutral Au38(SC6H13)24 monolayer-protected clusters (MPCs), following excitation of the mixed 15 875 cm-1 charge transfer resonance, were studied using femtosecond transient absorption (fsTA) and two-dimensional electronic spectroscopy (2DES). The excited carriers relax by three different mechanisms, including an ∼100 fs HOMO-12/-13 to HOMO-4/-6 hole transfer, picosecond HOMO-4/-6 to HOMO hole transfer, and subsequent electron-hole recombination that persisted beyond the hundreds of picoseconds measurement range. The fsTA data revealed two transient bleach components at 15 820 and 15 625 cm-1, where the lower frequency component exhibited a delayed first-order buildup of 80 ± 25 fs that matched the decay of the high-energy bleach component (110 ± 45 fs). These results suggested that the excited charge carriers internally relax within the exited-state manifold in ≈100 fs. 2DES resolved multiple electronic fine-structure transient peaks that spanned excitation frequencies ranging from 15 500 to 16 100 cm-1. State-to-state dynamics were understood by the analysis of time-dependent 2DES transient signal amplitudes at numerous excitation-detection frequency combinations. An off-diagonal cross peak at 15 825-15 620 cm-1 excitation-detection signified the HOMO-12/-13 to HOMO-4/-6 hole transfer process. The lowest-frequency (15 620 cm-1) 2DES diagonal fine-structure peak exhibited instantaneous amplitude but intensified following a 75 ± 10 fs buildup when compared to diagonal peaks at higher frequencies. This observation indicated that the charge transfer resonance in Au38(SC6H13)24 MPCs is comprised of several electronic transitions of unique spectral weights, which may result from different orbital contributions associated with specific cluster domains. The use of 2DES in combination with structurally precise MPCs can provide a platform for understanding structure-dependent electronic dynamics in metal nanoclusters and technologically important metal-chalcogenide interfaces.

Hospital admissions for stroke and bleeding in Hounslow following a quality improvement initiative.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia. Undiagnosed and poorly managed AF increases risk of stroke. The Hounslow AF quality improvement (QI) initiative was associated with improved quality of care for patients with AF through increased detection of AF and appropriate anticoagulation. This study aimed to evaluate whether there has been a change in stroke and bleeding rates in the Hounslow population following the QI initiative. METHODS: Using hospital admissions data from January 2011 to August 2018, interrupted time series analysis was performed to investigate the changes in standardised rates of admission with stroke and bleeding, following the start of the QI initiative in October 2014. RESULTS: There was a 17% decrease in the rate of admission with stroke as primary diagnosis (incidence rate ratio (IRR) 0.83; 95% CI 0.712 to 0.963; p<0.014). There was an even larger yet not statistically significant decrease in admission with stroke as primary diagnosis and AF as secondary diagnosis (IRR 0.75; 95% CI 0.550 to 1.025; p<0.071). No significant changes were observed in bleeding admissions. For each outcome, an additional regression model including both the level change and an interaction term for slope change was created. In all cases, the slope change was small and not statistically significant. CONCLUSION: Reduction in stroke admissions may be associated with the AF QI initiative. However, the immediate level change and non-significant slope change suggests a lack of effect of the intervention over time and that the decrease observed may be attributable to other events.

Characterization of Gene Repression by Designed Transcription Activator-like Effector Dimer Proteins.

Gene regulation by control of transcription initiation is a fundamental property of living cells. Much of our understanding of gene repression originated from studies of the Escherichia coli lac operon switch, in which DNA looping plays an essential role. To validate and generalize principles from lac for practical applications, we previously described artificial DNA looping driven by designed transcription activator-like effector dimer (TALED) proteins. Because TALE monomers bind the idealized symmetrical lac operator sequence in two orientations, our prior studies detected repression due to multiple DNA loops. We now quantitatively characterize gene repression in living E. coli by a collection of individual TALED loops with systematic loop length variation. Fitting of a thermodynamic model allows unequivocal demonstration of looping and comparison of the engineered TALED repression system with the natural lac repressor system.

Using a pharmacist-community health worker collaboration to address medication adherence barriers.

OBJECTIVE: Pharmacists are positioned to evaluate and educate patients regarding medication adherence; however, opportunities exist to leverage a collaborative approach in eliciting barriers encountered by patients, especially in minority groups. Community health workers (CHWs) are individuals from the communities who form relationships with patients and help increase their access to health care resources. This study aimed to evaluate the effectiveness of a collaboration between CHWs and pharmacists in identifying and addressing medication adherence barriers faced by hypertensive patients. METHODS: After receiving training in medication therapy management support, CHWs from the South East American Indian Council collaborated with students and pharmacists from the Center for Quality Medication Management at the University of Florida to identify and address medication adherence barriers encountered by hypertensive patients who were mainly Native American or black. The CHWs documented information from the patient interviews during the initial and follow-up visits. The team collaborated to identify intervention opportunities on the basis of the adherence barriers identified. Follow-up visits were conducted to measure progress. RESULTS: Thirty-three hypertensive patients with or without diabetes were included in the study. The pharmacists, in partnership with the CHWs, offered 149 interventions related to medication adherence barriers. The most commonly identified barriers included forgetfulness, adverse effects, and knowledge concerns. By the final visits, 75.6% of the barriers related to antihypertensive medications and 63.9% of the barriers related to antidiabetic medications were resolved. In addition, a paired t test indicated a significant difference in the mean blood pressure values (P = 0.006 for systolic and P = 0.008 for diastolic) recorded at the initial (mean = 136/85.7 mm Hg) and final (mean = 130.1/81.2 mm Hg) visits. CONCLUSION: The findings of this pilot project support the collaboration between pharmacists and CHWs to help improve medication adherence and patient outcomes. Additional research is recommended to validate these study findings.

Opportunities and responsibilities for pharmacists to improve their effectiveness in addressing medication adherence through culturally sensitive collaborations with community health workers.

OBJECTIVES: Despite progress in addressing health disparities among vulnerable populations, minority populations are at risk for chronic health conditions associated with multiple determinants of health, which affects their health status and access to care. We offer a potential solution, which creates an unconventional medical team between a pharmacist and a community health worker (CHW). We explore weaknesses and challenges in our medication use system in the context of adherence as a drug therapy problem, the role of culture in shaping medication use, and finally offer a unique paradigm for a collaborative interprofessional team consisting of CHWs and pharmacists. SUMMARY: Medication adherence is far from optimal, especially in minority ethnic populations. Members of an ethnic group may acquire beliefs about illness consistent with their culture's shared customs. These findings intimate that ethnocultural minority groups may have their own remedies for illness that shape their decision to use medications as prescribed. An interprofessional team in which CHWs and pharmacists collaborate offers an opportunity to improve the effectiveness of pharmacists to address adherence-related problems, especially among minority populations in which culturally determined beliefs can shape medication use decisions. This approach holds promise because CHWs are usually embedded within the community in which their patients live, having experienced the same life experiences. These shared experiences may lead CHWs to uncover medication use practices that pharmacists are not able to discover on their own because the relationship with their patients is often not authentic, which, for many minority patients, can only be established through shared experiences. CONCLUSION: This paper argues that creating teams of CHWs and pharmacists will help address challenges in achieving health equity and health disparities among vulnerable populations in the medication use system.