Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.

PURPOSE: Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion. METHODS: We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex. RESULTS: A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001). CONCLUSIONS: There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.

Chronological trends in the causation of malignant mesothelioma: Fiber burden analysis of 619 cases over four decades.

Malignant mesothelioma is a relatively rare malignancy with a strong association with prior asbestos exposure. A percentage of cases is not related to asbestos, and fiber analysis of lung tissue is a useful methodology for identifying idiopathic or spontaneous cases. We have performed fiber analyses in more than 600 cases of mesothelioma over the past four decades and were interested in looking for trends in terms of fiber types and concentrations as well as percentages of cases not related to asbestos. Demographic information was also considered including patient age, gender, and tumor location (pleural vs. peritoneal). The histologic pattern of the tumor and the presence or absence of pleural plaques or asbestosis were noted. Fiber analysis was performed in 619 cases, using the sodium hypochlorite technique for digestion of lung tissue samples. Asbestos bodies were counted by light microscopy (LM) and coated and uncoated fibers by scanning electron microscopy (EM). The results were stratified over four decades. Trends that were observed included increasing patient age, increasing percentage of women, increasing percentage of peritoneal cases, and increasing percentage of epithelial histological type. There was a decreasing trend in the percentage of patients with concomitant asbestosis (p < 0.001). The percentage of cases with an elevated lung asbestos content decreased from 90.5% in the 1980s to 54.1% in the 2010s (p < 0.001). This trend also held when the analysis was limited to 490 cases of pleural mesothelioma in men (91.8% in the 1980s vs. 65.1% in the 2010s). There was a decrease in the median asbestos body count by LM from 1390 asbestos bodies per gram of wet lung in the 1980s to 38 AB/gm in the 2010s. Similar trends were observed for each of the asbestos fiber types as detected by EM. We conclude that there has been a progressive decrease in lung fiber content of mesothelioma patients during the past four decades, with an increasing percentage of cases not related to asbestos and an increase in median patient age.

Impact of Education and Data Feedback on Antibiotic Prescribing for Urinary Tract Infections in the Emergency Department: An Interrupted Time-Series Analysis.

BACKGROUND: Urinary tract infections (UTIs) are often misdiagnosed or treated with exceedingly broad-spectrum antibiotics, leading to negative downstream effects. We aimed to implement antimicrobial stewardship (AS) strategies targeting UTI prescribing in the emergency department (ED). METHODS: We conducted a quasi-experimental prospective AS intervention outlining appropriate UTI diagnosis and management across 3 EDs, within an academic and 2 community hospitals, in North Carolina, United States. The study was divided into 3 phases: a baseline period and 2 intervention phases. Phase 1 included introduction of an ED-specific urine antibiogram and UTI guideline, education, and department-specific feedback on UTI diagnosis and antibiotic prescribing. Phase 2 included re-education and provider-specific feedback. Eligible patients included adults with an antibiotic prescription for UTI diagnosed in the ED from 13 November 2018 to 1 March 2021. Admitted patients were excluded. The primary outcome was guideline-concordant antibiotic use, assessed using an interrupted time-series regression analysis with 2-week intervals. RESULTS: Overall, 8742 distinct patients with 10 426 patient encounters were included. Ninety-two percent of all encounters (n = 9583) were diagnosed with cystitis and 8.1% with pyelonephritis (n = 843). There was an initial 15% increase in guideline-concordant antibiotic prescribing in phase 1 compared with the preintervention period (incidence rate ratio [IRR], 1.15; 95% confidence interval [CI], 1.03-1.29). A significant increase in guideline-concordant prescriptions was seen with every 2-week interval during phase 2 (IRR, 1.03; 95% CI, 1.01-1.04). CONCLUSIONS: This multifaceted AS intervention involving a guideline, education, and provider-specific feedback increased guideline-concordant antibiotic choices for treat-and-release patients in the ED.

High-dose, high-frequency ustekinumab therapy for patients with severe hidradenitis suppurativa.

In this case series, ustekinumab therapy demonstrated efficacy in some patients with severe hidradenitis suppurativa previously treated with adalimumab and/or infliximab. Larger prospective studies are needed to evaluate ustekinumab as a treatment option for recalcitrant hidradenitis suppurativa.

Medical adhesive allergens: Retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2018.

BACKGROUND: Identification of allergens causing medical adhesive contact allergy is difficult. OBJECTIVE: To characterize the demographics, clinical characteristics, patch test results, and occupational data for North American Contact Dermatitis Group patients with medical adhesive contact allergy. METHODS: A retrospective study of 43,722 North American Contact Dermatitis Group patients patch tested from 2001 to 2018 with medical adhesive (tapes/bandaids/adhesive aids/suture glue) sources, positive patch test results, and final primary diagnoses of allergic contact dermatitis. RESULTS: In total, 313 (0.7%) patients met the inclusion criteria. Compared with other patients with final primary diagnoses of allergic contact dermatitis, patients with a medical adhesive allergy were less likely to be male (odds ratio, 0.58; 95% CI, 0.45-0.77) and/or aged >40 years (odds ratio, 0.76; 95% CI, 0.60-0.96). The most common North American Contact Dermatitis Group screening series allergens were colophony (80.7%), balsam of Peru (3.9%), 2-hydroxyethyl methacrylate (2.7%), and carba mix (2.7%). One-fourth of the patients (79/313, 25.2%) had positive patch test reactions to supplemental allergens/materials, and 54 (17.3%) of the 313 patients only had reactions to supplemental allergens/materials. LIMITATIONS: Results of comprehensive patch testing may be prone to referral population selection bias and may not be representative of the general dermatology population. CONCLUSION: Colophony was the most common allergen. Supplemental allergens and materials should be tested in the evaluation of a suspected medical adhesive contact allergy.

Comparison of intermittent versus continuous infusion antihypertensives in acute ischemic stroke.

BACKGROUND: The optimal approach to blood pressure (BP) management in acute ischemic stroke remains unclear. The purpose of this study was to determine if an intermittent (labetalol or hydralazine) or continuous infusion (nicardipine or clevidipine) antihypertensive strategy facilitated timelier alteplase administration. METHODS: Patients ≥18 years who presented to the emergency department (ED) between September 1, 2013 and August 31, 2020, received alteplase for acute ischemic stroke, and required BP management with an intravenous antihypertensive were included in this multicenter, retrospective cohort study. Exclusion criteria were initial administration of a non-study antihypertensive, initial study antihypertensive administration >2 hours prior to or any time following alteplase, or receipt of both an intermittent and continuous infusion antihypertensive prior to alteplase. The primary endpoint was the time from ED presentation to alteplase administration. RESULTS: During the study period, 122 patients received an intermittent antihypertensive and 57 patients received a continuous infusion antihypertensive. The median door-to-needle time was 53 minutes for patients who received an intermittent antihypertensive compared to 57 minutes for those who received a continuous infusion antihypertensive (p=0.17). Secondarily, the proportion of patients who achieved the BP target <185/110 mmHg within 15 minutes of initial antihypertensive administration and the incidence of adverse events were similar between treatment groups. In cost analysis, intermittent antihypertensives were less expensive than continuous infusion antihypertensives ($2.20 vs. $71.40). CONCLUSIONS: Among patients with acute ischemic stroke and uncontrolled BP, the initial use of an intermittent or continuous infusion antihypertensive did not significantly impact the time to alteplase administration.

Impact of pharmacist outreach on glucagon prescribing.

BACKGROUND: Hypoglycemia is a major limiting factor in the glycemic management of diabetes. As a method of treating hypoglycemia, the American Diabetes Association recommends glucagon to be prescribed for all individuals at increased risk of clinically impactful hypoglycemia. Glucagon Emergency Kits have been shown to reduce emergency department visits and overall health care costs. Despite these known benefits, glucagon continues to be underprescribed. Previous pharmacist-led interventions embedded in a single clinic have been shown to positively affect the rate of glucagon prescribing in patients with diabetes. OBJECTIVE: This study aimed to compare the rate of glucagon prescribing between quality improvement remote pharmacist outreach to multiple primary care and endocrinology specialty clinics and the control group in 1 month following a pharmacist-led provider outreach. METHODS: This was a single-center, 2-arm study with a simple randomization design. RESULTS: On pharmacist outreach, 61 of 109 patients (56.0%) in the outreach group were prescribed a glucagon product within 1 month of their primary care provider (PCP) or endocrinology appointment compared with 1 of 113 (0.9%) of patients in the control group (P < 0.001). Glucagon prescribing occurred in 25 of 35 Black patients (71.4%) compared with 36 of 73 white patients (49.3%) in the outreach group. Glucagon prescribing was associated with race (P = 0.03; chi-square test). CONCLUSIONS: The pharmacist-led provider outreach before a PCP or endocrinology appointment has a positive and statistically significant impact on glucagon prescribing rates. The pharmacist outreach had a higher impact on Black patients than white patients, possibly because of a lower rate of glucagon prescribing in Black patients before the outreach.

Contact dermatitis associated with preservatives: Retrospective analysis of North American Contact Dermatitis Group data, 1994 through 2016.

BACKGROUND: Preservatives are often necessary components of commercial products. Large-scale North American studies on preservative allergy are limited. OBJECTIVE: To evaluate demographics, positive patch test reactions (PPTRs), clinical relevance, and trends for preservatives tested by the North American Contact Dermatitis Group. METHODS: We conducted a retrospective cross-sectional analysis of North American Contact Dermatitis Group patch testing results of preservatives from 1994 through 2016. RESULTS: A total of 50,799 patients were tested; 11,338 (22.3%) had a PPTR to at least 1 preservative. The most frequent reactions were to methylisothiazolinone 0.2% aqueous (aq) (12.2%), formaldehyde 2% aq (7.8%), formaldehyde 1% aq (7.8%), quaternium-15 2% petrolatum (pet) (7.7%), and methyldibromo glutaronitrile/phenoxyethanol 2% pet (5.1%). Paraben mix 12% pet (1%), iodopropynyl butylcarbamate 0.1% pet (0.4%), benzyl alcohol 1% pet (0.3%), and phenoxyethanol 1% pet (0.2%) had the lowest PPTRs. Linear regression analysis of preservatives tested showed that only methylchloroisothiazolinone/methylisothiazolinone 0.01% aq (parameter estimate, 0.42; 95% CI, 0.17-0.66; P < .005) had a significant increase in PPTRs over time. LIMITATIONS: Collected variables are dependent on clinical judgment. Results may be prone to referral selection bias. CONCLUSIONS: This large North American study provides insight on preservative PPTRs and trends from 1994 through 2016.

Characterization of Isavuconazole serum concentrations after enteral feeding tube administration in a hospitalized cohort: A case series.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections often occur in patients with comorbidities that complicate oral administration. Serum concentrations of isavuconazole were characterized after enteral tube administration. CASE DESCRIPTION: Thirteen of 14 isavuconazole concentrations were >1 mg/dl (median 1.6 mg/dl) among those receiving enteral tube administration, which was comparable to intravenous (median 1.9 mg/dl). Higher concentrations were observed during oral administration (median 3 mg/dl). WHAT IS NEW AND CONCLUSION: Administration of isavuconazole via tube resulted in concentrations comparable to FDA-approved routes of administration. This route may be feasible and appropriate for select patients.

Impact of a Real-Time, Pharmacist-Led, Intensive Care Unit-Based Feedback Intervention on Analgesia and Sedation Quality Among Mechanically Ventilated Patients.

BACKGROUND: Consensus guidelines for pain, agitation, and delirium (PAD) in mechanically ventilated patients recommend maintaining a light level of sedation. LOCAL PROBLEM: Consistent attainment of target PAD assessments in mechanically ventilated ICU patients is often challenging. METHODS: This is a single-center, prospective study. INTERVENTIONS: In the intervention group, a pharmacist provided weekly feedback to nurses on their success in achieving target PAD assessments compared with a historical cohort without feedback. RESULTS: Overall, 478 patients and 205 nurses were included. The odds of having weekly Richmond Agitation-Sedation Scale (RASS) score, pain score goals, and Confusion Assessment Method for the ICU (CAM-ICU) negative assessments at goal between the intervention and control groups fluctuated over time without a discernible trend. CONCLUSION: The provision of weekly feedback to nurses on PAD nursing assessments by a pharmacist did not impact the achievement of PAD goals among critically ill mechanically ventilated patients.

Meta-analysis of number needed to treat for diagnosis of melanoma by clinical setting.

OBJECTIVE: To provide a formal statistical comparison of the efficacy of melanoma detection among different clinical settings. METHODS: A systematic review and meta-analysis of all relevant observational studies on number needed to treat (NNT) in relation to melanoma was performed in MEDLINE. We performed a random-effects model meta-analysis and reported NNTs with 95% confidence intervals (CIs). The subgroup analysis was related to clinical setting. RESULTS: In all, 29 articles including a total of 398,549 biopsies/excisions were analyzed. The overall NNT was 9.71 (95% CI, 7.72-12.29): 22.62 (95% CI, 12.95-40.10) for primary care, 9.60 (95% CI, 6.97-13.41) for dermatology, and 5.85 (95% CI, 4.24-8.27) for pigmented lesion specialists. LIMITATIONS: There is heterogeneity in data reporting and the possibility of missing studies. In addition, the incidence of melanoma varies among clinical settings, which could affect NNT calculations. CONCLUSION: Pigmented lesion specialists have the lowest NNT, followed by dermatologists, suggesting that involving specialists in the diagnosis and treatment of pigmented skin lesions can likely improve patient outcomes.

Evaluation of thiamine for the prevention of ifosfamide-induced encephalopathy.

STUDY OBJECTIVE: To determine whether thiamine prophylaxis decreases the incidence of ifosfamide-induced encephalopathy in patients receiving ifosfamide for the treatment of lymphoma. DESIGN: Retrospective, multi-center, cohort study. PATIENTS: A total of 73 patients who received 187 total cycles of ifosfamide, carboplatin, and etoposide chemotherapy for the treatment of lymphoma were included in this study. Forty-four of these patients (114 cycles) were included in the no-thiamine group and 29 (65 cycles) in the thiamine group. MEASUREMENTS AND MAIN RESULTS: The incidence of ifosfamide-induced encephalopathy was measured using the Common Terminology Criteria for Adverse Events and documentation in the patient chart. Regarding the primary endpoint of ifosfamide-induced encephalopathy, eight patients (18.2%) in the no-thiamine group and three patients (10.3%) in the thiamine group experienced an event (p = 0.5087). No patient experienced more than one neurotoxic event. CONCLUSION: There was no significant difference found in the incidence of ifosfamide-induced encephalopathy with the addition of thiamine prophylaxis in patients receiving ifosfamide, carboplatin, and etoposide-based chemotherapy regimens for lymphoma. Larger, prospective studies assessing the use of thiamine prophylaxis in this patient population are warranted to better assess its impact on the incidence of ifosfamide-induced encephalopathy.

Outcomes of surgical treatment for hemangiomas.

OBJECTIVE: To quantify complications and rates of adverse events associated with surgical excision of hemangiomas in children using a national surgical database. DATA SOURCE: Pediatric American College of Surgeons (ACS) National Surgical Quality Improvement Program® (ACS NSQIP® -pediatric), years 2012-2016. METHODS: Subjects included children under 18 years with a postoperative diagnosis of International Classification of Diseases (ICD), 9th revision code: 228.00 and 228.01, or ICD 10 codes D18.00 and D18.01-hemangioma, any site and hemangioma, of skin and subcutaneous tissue. RESULTS: A total of 1180 patients were included. The median age was 3.2 years (interquartile range [IQR] 1.2 to 6.4 years old). No occurrences of deep incisional surgical site infection, nerve injury, mortality, sepsis, septic shock, or blood stream infections were noted. In multivariate analysis, age ≤ 3 years and advanced American Society of Anesthesiologists class were significant predictors of adverse events (P = 0.035 and 0.001, respectively). CONCLUSIONS: For children with infantile hemangioma who fail to respond or have an incomplete response to medical therapy, surgical resection may be a relatively safe treatment alternative. Children older than 3 years of age with hemangiomas had less surgical adverse events than younger children. Overall, however, the surgical complications rates were low and deemed relatively minor.

National estimations of airway foreign bodies in children in the United States, 2000 to 2009.

OBJECTIVE: Identify risk factors associated with airway foreign bodies in children in the United States and report observed trends over time. DATA SOURCE: KID database (2000-2009). METHODS: ICD-9-CM codes for airway foreign bodies were used to identify patients. Risk factors were used for univariate analysis and a multivariate model to identify any increased risk of mortality. These factors were then also trended over time. RESULTS: Children with airway foreign bodies demonstrate similar risk factors as previously reported, such as male gender, age less than five years and lack of private insurance. The weighted mortality rate for paediatric inpatients with airway foreign bodies was about 2.75%. Fortunately, the rate remained relatively unchanged from 2000 to 2009. Geographically, urban hospital settings appeared to be more affected. Increased risks of mortality were noted for older age, urban hospital setting and teaching hospital status. CONCLUSIONS: Our findings confirm previous findings and identified that the diagnosis of airway foreign bodies in children were associated with male gender, age <5 years, lack of private insurance and geographic location in an urban setting. Further investigation may be warranted to provide clarity on other factors found to have increased association with mortality for quality improvement.

National Characteristics of Lymphatic Malformations in Children: Inpatient Estimates and Trends in the United States, 2000 to 2009.

With ever increasing demands to manage finite resources for health care utilization, we performed an investigation to identify inpatient clinical characteristics and trends in children with lymphatic malformations using the Kids' Inpatient Database, years 2000 to 2009, to help identify populations best suited for resource deployment. Subjects included children 18 years and below with International Classification of Diseases (ICD), ninth revision code: 228.1-lymphangioma, any site. In the United States, between 2000 and 2009, inpatient pediatric patients with lymphatic malformations most commonly affected children aged 3 years and younger, urban hospital locations, and the South and West regions. There was no significant change in age of children with lymphatic malformations or the distribution of their age from year to year, P=0.948 and 0.4223, respectively. No significant evidence for seasonal variation or effect on inpatient admission was identified, P=0.7071. A great majority of admissions (>96%) were in urban locations across each year. There was also no significant change in breakdown of admissions by geographic location, P=0.7133. Further investigation may help to elucidate how to improve access to multidisciplinary vascular anomalies teams to optimize care for these children with unique and complex lymphatic malformations.

ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate.

In order to propagate a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. To systematically identify genes that modulate cancer cell survival under stresses, we performed genome-wide shRNA screens under hypoxia or lactic acidosis. We discovered that genetic depletion of acetyl-CoA carboxylase (ACACA or ACC1) or ATP citrate lyase (ACLY) protected cancer cells from hypoxia-induced apoptosis. Additionally, the loss of ACLY or ACC1 reduced levels and activities of the oncogenic transcription factor ETV4. Silencing ETV4 also protected cells from hypoxia-induced apoptosis and led to remarkably similar transcriptional responses as with silenced ACLY or ACC1, including an anti-apoptotic program. Metabolomic analysis found that while α-ketoglutarate levels decrease under hypoxia in control cells, α-ketoglutarate is paradoxically increased under hypoxia when ACC1 or ACLY are depleted. Supplementation with α-ketoglutarate rescued the hypoxia-induced apoptosis and recapitulated the decreased expression and activity of ETV4, likely via an epigenetic mechanism. Therefore, ACC1 and ACLY regulate the levels of ETV4 under hypoxia via increased α-ketoglutarate. These results reveal that the ACC1/ACLY-α-ketoglutarate-ETV4 axis is a novel means by which metabolic states regulate transcriptional output for life vs. death decisions under hypoxia. Since many lipogenic inhibitors are under investigation as cancer therapeutics, our findings suggest that the use of these inhibitors will need to be carefully considered with respect to oncogenic drivers, tumor hypoxia, progression and dormancy. More broadly, our screen provides a framework for studying additional tumor cell stress-adaption mechanisms in the future.