Stability and compatibility of an intramuscular fetal anesthetic cocktail for fetal intervention.

INTRODUCTION: To evaluate chemical stability and physical compatibility when combining fentanyl, rocuronium, and atropine in a fixed ratio to support intramuscular drug delivery during fetal intervention and surgery. METHODS: A highly concentrated combination of fentanyl, rocuronium, and atropine was created based on common prescribing practices at a maternal fetal care center. Chemical stability testing was completed using liquid chromatograph mass spectrometry-mass spectrometry (LC/MS-MS) to detect and quantitate atropine, rocuronium, and fentanyl, with fentanyl-d5 being an internal standard at 6-, 12, 24-, and 36-hours following sample preparation. Physical compatibility testing was completed using United State Pharmacopeia (USP)<788> recommended analytical technique of light obscuration (LO) in addition to novel backgrounded membrane imaging (BMI) at 6- and 24-hours following sample preparation. Physical compatibility was determined using USP<788> particle count limits for both techniques. RESULTS: Based on LC/MS-MS results, the samples retained expected medication concentrations at all time points tested. For physical compatibility testing, the particle counts met criteria to be considered compatible per USP<788> large volume particle count thresholds at 6 hours by both methods but exceeded tolerable thresholds at 24 hours. DISCUSSION/CONCLUSION: The combination of rocuronium, fentanyl, and atropine for intramuscular fetal administration are physically compatible and chemically stable for 6 hours.

Successful and Rapid Reduction in Neurosedative and Analgesic Medications in Complex Infants with Severe Bronchopulmonary Dysplasia After Tracheostomy Placement: Experience with 24-hour Propofol Infusions.

Infants with severe bronchopulmonary dysplasia may require high doses of neurosedative medications to ensure pain control and stability following tracheostomy placement. Subsequent weaning of these medications safely and rapidly is a challenge. We describe a 24-hour propofol infusion to reduce neurosedative medications in 3 high-risk infants following tracheostomy placement.

Successful Management of Fetal Torsades de Pointes and Long QT Syndrome by a Cardio-Obstetrical Team.

A 32-week fetus with tachycardia and bradycardia, diagnosed with torsades de pointes, atrioventricular block, and sinus bradycardia due to a de novo KCNH2 mutation was successfully managed by a cardio-obstetrical team. Maternal/fetal pharmacogenomic testing resulted in appropriate drug dosing without toxicity and delivery of a term infant in sinus rhythm.

Suicide risk following ED presentation with self-harm varies by hospital.

BACKGROUND: Patients presenting to Emergency Department (ED) with self-harm are recognized to be at high risk of suicide and other causes of death in the immediate period following ED presentation. It is also recognized that there is a large variation in the management and care pathways that these patients experience at EDs. AIMS: This study asks if there is a significant variation in mortality risk according to hospital attended and if this is explained by differences in care management. METHODS: Population-wide data from the Northern Ireland Registry of Self-Harm from April 2012 were linked with centrally held mortality records to December 2019, providing data on self-harm type and ED care. Cox proportional hazards models analyzed mortality risk, coded as suicide, all-external causes and all-cause mortality. RESULTS: Analysis of the 64,350 ED presentations for self-harm by 30,011 individuals confirmed a marked variation across EDs in proportion of patients receiving mental health assessment and likelihood of admission to general and psychiatric wards. There was a significant variation in suicide risk following attendance according to ED attended with the three-fold range between the lowest (HRadj 0.32 95% CIs 0.16, 0.67) and highest. These differences persisted even after adjustment for patient characteristics, variation in types of self-harm, and care management at the ED. CONCLUSIONS: This study suggests that while the management of self-harm cases in the ED is important, it is the availability and access to, and level of engagement with, the subsequent management and care in the community rather than the immediate care at EDs that is most critical for patients presenting to ED with self-harm. However, the initial care in ED is an important gateway in initiating referrals to these services.

Mortality risk following self-harm in young people: a population cohort study using the Northern Ireland Registry of Self-Harm.

BACKGROUND: Self-harm is a recognised predictor of suicide and is most common in those aged under 25 years. The aims of this study were to describe the characteristics of young people who present with self-harm; quantify the risk of suicide and other causes of death during follow up, and to identify factors associated with mortality risk. METHODS: The Northern Ireland Registry of Self-Harm (NIRSH) is a national registry capturing complete data on all presentations made to the 12 Emergency Departments (EDs) in Northern Ireland (NI). Data relating to self-harm presentations registered in the NIRSH between 2012 and 2015 were linked to primary care registrations and death records up until 31st December 2018. Logistic regression was employed to examine the factors associated with self-harm. Cox regression was used to estimate mortality risk following self-harm and explore the associated risk factors. RESULTS: The cohort consisted of 390,740 individuals aged 10-24 years registered with a General Practitioner (GP) in NI. During follow-up, 4,450 individuals presented with self-harm. Rates of self-harm were highest in females, those aged 20-24 years (ORadj  = 3.53, 95% CI 3.28-3.80, p < .001), and in the most deprived areas (ORadj  = 2.71, 95% CI 2.45-2.99, p < .001). Thirty five individuals who presented with self-harm died by suicide, accounting for 23% of all suicide deaths in the cohort. Suicide risk was increased 19-fold in those who presented with self-harm after adjustment for age, sex and area-level factors (HRadj  = 19.00, 95% CI 12.80-28.21, p < .001). Increased suicide risk was observed in males (HRadj  = 2.04, 95% CI 0.99-4.23, p = .05) and those using more violent methods of self-injury (HRadj  = 3.89, 95% CI 1.65-9.13, p < .001). CONCLUSIONS: Young people who self-harm are at a significantly greater risk of suicide. Almost a quarter of young people who died by suicide in NI had presented to EDs with self-harm, highlighting that the ED may provide a nodal point of intervention among a typically hard to identify and reach population.

Psychosocial and Cultural Processes Underlying the Epidemiological Paradox within U.S. Latino Sexual Risk: A Systematic Review.

According to the epidemiological paradox, less acculturated Latina/o youth display fewer sexual risk behaviors. A systematic review was performed on psychosocial and cultural mechanisms potentially underlying the epidemiological paradox in sexual risk behaviors of U.S. Latina/o youth across acculturation measures (between January 2000 to October 2022). Thirty-five publications (n = 35) with forty-eight analyses of underlying mechanisms met the inclusion criteria. Thirty-one results from twenty-three publications found supporting evidence that one of the five factors was an underlying mechanism in the epidemiological paradox (n = 13 parenting practices, n = 4 peer influences, n = 4 familismo values, n = 4 religiosity, n = 6 traditional gender norms) as, generally protective, mediators or moderators in the link between acculturation and sexual risk behaviors. Studies varied in the sexual risk behavior examined and measurement of acculturation, but primarily employed cross-sectional designs and recruited samples through schools. Mechanisms that enhance close ties and unity of the family, such as those of familismo values and positive parenting, reduce the likelihood of sexual risk behaviors as Latina/o youth become more acculturated. Future directions are discussed which may provide guidance for risk prevention and intervention.

Physical Compatibility of Y-site Pediatric Drug Administration: A Call for Question of US Pharmacopeia Standards.

OBJECTIVE: To evaluate the physical intravenous Y-site compatibility of 29 combinations of medications at commonly used pediatric concentrations using both existing and novel techniques. METHODS: Medication combinations included were selected by a varied group of pediatric inpatient pharmacists, and then assessed by 3 independent reviewers for existing literature. For each combination, 2 different medications were mixed together in a 1:1 ratio and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then analyzed using the US Pharmacopeia (USP) <788> recommended analytical technique of light obscuration (LO) in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP chapter <788> large volume particle count limits for all techniques. RESULTS: A total of 29 different medication combinations were studied. Five combinations met criteria for compatibility by all 3 techniques. The remaining 24 combinations reached the threshold to be considered incompatible by at least 1 of the 3 techniques. Light obscuration, BMI, and FI identified 14%, 59%, and 76% of combinations as incompatible, respectively. All samples deemed incompatible by LO were also incompatible by at least 1 of the other 2 techniques. Flow imaging and BMI results agreed in 69% of samples tested. CONCLUSIONS: Most combinations tested were found to be incompatible by at least 1 of the 3 instruments used. Light obscuration appears to have reduced accuracy for identifying particulate resulting in physical medication incompatibility when compared with the novel techniques of FI and BMI.

Physical compatibility of medications with concentrated neonatal and pediatric parenteral nutrition: A simulated Y-site drug compatibility study.

BACKGROUND: The physical intravenous Y-site compatibility of 15 different medications with highly concentrated neonatal and pediatric parenteral nutrition (PN) compounds is described, using existing and novel methods. METHODS: PN formulations were developed based on common prescribing practices in a 400+-bed freestanding children's hospital. Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with both pediatric and neonatal PN formulations and incubated at room temperature for 4 h to simulate Y-site administration. Samples were then analyzed using the light obscuration (LO) technique, as recommended by United States Pharmacopeia (USP) chapter 788, in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP 788 particle count limits for all techniques. RESULTS: Most combinations were found to be compatible per USP 788 thresholds. Pediatric PN was incompatible by at least two methods with cisatracurium 2 mg/ml, sildenafil 0.8 mg/ml, furosemide 10 mg/ml, and ketamine 10 mg/ml. Neonatal PN was incompatible by at least two methods with cisatracurium 2 mg/ml and furosemide 10 mg/ml. Overall, results for 20 of the 30 combinations (66%) agreed across all three methods. FI and BMI results agreed for 22 of 30 combinations. LO agreed with FI in 25 of 30 combinations, and BMI and LO results agreed in 23 of 30 combinations. CONCLUSION: Most combinations tested were found to be compatible across all methods. Novel methods of FI and BMI seem useful to further evaluate LO findings and improve accuracy of particle counts when assessing PN-medication combinations.

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods.

In hospitals, often drug products in intravenous (IV) bags are transported via pneumatic tube systems (PTS). The goal of this study was to evaluate the effects of such transportation of protein products on particle formation in polyvinyl chloride (PVC) and polyolefin (PO) IV bags, containing either IV saline or dextrose. We studied intravenous immunoglobulin (IVIG) and a monoclonal antibody (mAb). Particles were quantified with flow imaging, light obscuration and nanoparticle tracking analysis. PTS transportation of IVIG caused large increases in protein particle concentrations, with much greater increases observed in saline than in dextrose. The increases were greater in IV solutions in PO than those in PVC bags. With the mAb, PTS transportation in saline caused increases in protein particle levels in PO bags, but not in PVC bags. Transportation in dextrose did not result in significant increases in mAb particle concentrations in IV bags made of either material. Overall, the results document that the PTS transportation can result in large increases in protein particles and that magnitude of these increases depends the protein itself, the bag material and the IV solution. The main conclusion is that protein products in IV solutions should not be transported in hospital PTS.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor. PATIENTS AND METHODS: A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC. The main parameters were safety and objective treatment response to selpercatinib. RESULTS: Six children (three males and three females, aged 3-12 years), four with MEN2B and two MEN2A, are reported. All had initial total thyroidectomy and extensive neck dissections but subsequently developed recurrent and progressive disease. All experienced an improvement in clinical symptoms with a concomitant biochemical response evidenced by significant fall in serum calcitonin and CEA concentrations. The fall in serum calcitonin was evident within 2 weeks of the start of selpercatinib, and responses were ongoing at a median follow-up of 13 months (range, 11-22 months). Four children with measurable radiological disease had good volume reduction. The most common adverse effects were transient but reversible grade 1 or 2 increase in alanine aminotransferase, serum bilirubin and constipation. No child required a dose modification or had to discontinue selpercatinib because of a drug-related adverse event. CONCLUSION: Selpercatinib has shown excellent therapeutic efficacy with minimal toxicity in children with MEN2 and progressive metastatic RET-mutated MTC.

Disparities in Breast Cancer Screening Uptake for Women With Mental Illness in the United Kingdom.

INTRODUCTION: Although there is evidence of disparities in breast cancer screening for women with mental illness in the U.S., there is a dearth of studies examining this association in the United Kingdom, where health care is provided free at the point of access. This population-based study examines the influence of mental illness, as assessed by the uptake of psychotropic medications, on breast screening uptake in the United Kingdom. METHODS: A cohort of 57,328 women identified from 2011 Census records within the Northern Ireland Longitudinal Study was followed through a single 3-year screening cycle (2011-2014) of the National Health Service Breast Screening Programme. Mental illness was identified by a receipt of psychotropic medication in the 3 months preceding screening invite. Individual- and household-level attributes were derived from Census records. Data were analyzed in 2019. RESULTS: More than a third of women received ≥1 prescription for psychotropic medication in the 3 months preceding screening invite. The odds of attendance in these individuals were reduced by 15% (OR=0.85, 95% CI=0.81, 0.88). Attendance was particularly low for women prescribed antipsychotics (OR=0.63, 95% CI=0.56, 0.70), anxiolytics (OR=0.61, 95% CI=0.57, 0.66), and hypnotics (OR=0.68, 95% CI=0.63, 0.72). CONCLUSIONS: These findings confirm the existence of significant disparities in breast screening uptake for women with mental illness. Targeted interventions are warranted to prevent avoidable breast cancer deaths in these individuals, especially given the increasing prevalence of mental illness.

Compatibility of medications with intravenous lipid emulsions: Effects of simulated Y-site mixing.

PURPOSE: To determine the physical intravenous Y-site compatibility of 19 commonly used medications at pediatric concentrations with 3 different types of lipid emulsion. METHODS: Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with lipid emulsions (Intralipid, Nutrilipid, and Smoflipid) and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then diluted with particle-free water and analyzed using the analytical technique of light obscuration recommended in United States Pharmacopeia (USP) general information chapter 729 (USP <729>). Physical compatibility was determined by measuring the percentage of fat residing in globules larger than 5 µm (PFAT5) per USP <729> recommendations. RESULTS: Most combinations tested were physically compatible based on USP <729> regulations. Incompatibilities differed for the different brands of lipid emulsion. The two combinations that met USP <729> criteria for physical incompatibility were cisatracurium 2 mg/mL with Intralipid and gentamicin 2 mg/mL with Smoflipid. CONCLUSION: Three different lipid emulsions were physically compatible at the Y site with the majority of medications tested. Data regarding Y-site compatibility for one lipid emulsion product cannot be safely extrapolated to another without additional testing.

Diuretic Use and Subsequent Electrolyte Supplementation in a Level IV Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the relationship between diuretic use, serum electrolyte concentrations, and supplementation requirements in infants admitted to the neonatal intensive care unit. METHODS: This was a single-center retrospective cohort study conducted in a freestanding children's hospital Level IV NICU. Data were collected for all infants younger than 6 months, admitted to the NICU between January 2015 and May 2017, who received 2 or more consecutive doses of furosemide, chlorothiazide, hydrochlorothiazide, and/or hydrochlorothiazide/spironolactone. The primary outcome was the composite of the incidence of electrolyte abnormalities and/or electrolyte supplementation requirement within 30 days of diuretic exposure. RESULTS: A total of 72 patients met inclusion criteria, with a median gestational age of 30 weeks. Overall, 92% of patients exposed to diuretics experienced derangement in at least 1 serum electrolyte and/or required electrolyte supplementation during diuretic therapy. Patients born at 36 to 41 weeks' gestational age, receiving thiazide diuretics, experienced a significantly lower rate of the primary outcome (37%, p ≤ 0.001). The most common electrolytes affected by diuretic use were potassium and bicarbonate, with the highest incidence of the primary outcome for potassium occurring in patients receiving furosemide (p = 0.0196). Last, the median total daily dose of chlorothiazide in patients with an adverse event was 15 mg/kg/day, compared with 10 mg/kg/day in patients without an adverse event (p = 0.0041). CONCLUSIONS: Use of diuretics in young infants is likely to cause electrolyte derangements and/or require electrolyte supplementation. Patients born at earlier gestational ages may be at higher risk for developing such adverse effects.

DEHP Nanodroplets Leached From Polyvinyl Chloride IV Bags Promote Aggregation of IVIG and Activate Complement in Human Serum.

Concerns regarding the impact of subvisible particulate impurities on the safety and efficacy of therapeutic protein products have led manufacturers to implement strategies to minimize protein aggregation and particle formation during manufacturing, storage, and shipping. However, once these products are released, manufacturers have limited control over product handling. In this work, we investigated the effect of di(2-ethylhexyl) phthalate (DEHP) nanodroplets generated in polyvinyl chloride (PVC) bags of intravenous (IV) saline on the stability and immunogenicity of IV immunoglobulin (IVIG) formulations. We showed that PVC IV bags containing saline can release DEHP droplets into the solution when agitated or transported using a pneumatic tube transportation system in a clinical setting. We next investigated the effects of emulsified DEHP nanodroplets on IVIG stability and immunogenicity. IVIG adsorbed strongly to DEHP nanodroplets, forming a monolayer. In addition, DEHP nanodroplets accelerated IVIG aggregation in agitated samples. The immunogenicity of DEHP nanodroplets and IVIG aggregates generated in these formulations were evaluated using an in vitro assay of complement activation in human serum. The results suggested DEHP nanodroplets shed from PVC IV bags could reduce protein stability and induce activation of the complement system, potentially contributing to adverse immune responses during the administration of therapeutic proteins.

Does poor mental health explain socio-demographic gradients in breast cancer screening uptake? A population-based study.

BACKGROUND: Research from the USA indicates disparities in breast cancer screening uptake for women with poor mental health. However, no attempt has been made to examine the contribution of poor mental health to socio-demographic variations in breast screening uptake. The current study aims to examine the impact of self-reported chronic poor mental health on attendance at breast screening in the UK, and to what extent this explains socio-demographic inequalities in screening uptake. METHODS: Breast screening records were linked to 2011 Census records within the Northern Ireland Longitudinal Study. This identified a cohort of 57 328 women who were followed through one 3-year screening cycle of the National Health Service Breast Screening Programme. Information on mental health status, in addition to other individual and household-level attributes, was derived from the 2011 Census. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of attendance at screening. RESULTS: 10.7% of women in the cohort reported poor mental health, and in fully adjusted analyses, these individuals were 23% less likely to attend breast screening (OR 0.77; 95% CI 0.73-0.82). Although poor mental health was a strong predictor of screening uptake, it did not explain the observed inequalities in uptake by socio-economic status, marital status, or area of residence. CONCLUSIONS: This study provides novel evidence of inequalities in breast screening uptake for women with chronic poor mental health in the UK. Targeted interventions are necessary to ensure equitable screening access and to enhance overall mortality benefit.

Disability as a predictor of breast cancer screening uptake: A population-based study of 57,328 women.

OBJECTIVE: Despite a growing body of evidence suggesting inequalities in breast cancer screening uptake in the United States for women with disabilities, few attempts have been made to examine whether this association applies to the United Kingdom. We conducted the first population-wide study investigating the impact of disability on uptake of breast cancer screening in Northern Ireland. METHODS: Breast screening records extracted from the National Breast Screening System were linked to the Northern Ireland Longitudinal Study. This identified a cohort of 57,328 women who were followed through one complete three-year screening cycle of the National Health Service Breast Screening Programme in Northern Ireland. The presence of disability was identified from responses to the 2011 Census. RESULTS: Within this cohort, 35.8% of women reported having at least one chronic disability, and these individuals were 7% less likely to attend compared with those with no disability (odds ratio 0.93; 95% confidence interval 0.89-0.98). Variation in the degree of disparity observed was evident according to the type and number of comorbid disabilities examined. CONCLUSION: This is the first population-wide study in Northern Ireland to identify disparities in breast screening uptake for women with chronic disabilities, in particular, those with multimorbidity. This is of particular concern, given the projected rise in the prevalence of disability associated with the ageing population.