A novel 2-step process for the management of inpatient beta-lactam allergy labels.

BACKGROUND: Inpatient beta-lactam allergy labels may increase the unnecessary use of aztreonam and non-beta-lactam antibiotics, which can then lead to more adverse events and increased health care costs, OBJECTIVE: To assess the impact of a novel 2-step process (medication history review followed by risk stratification) on rates of beta-lactam delabeling, aztreonam use, and desensitizations on pediatric, adult, and obstetrics inpatients at a tertiary academic center. METHODS: We prospectively collected data on 700 patients who received inpatient consultation from the Beta-Lactam Allergy Evaluation Service between August 2021 and July 2022. Patients were delabeled either by medication review alone, drug challenge alone if with a low-risk history, or penicillin skin test followed by drug challenge if with a high-risk history. Generalized linear regression modeling was used to compare aztreonam days of therapy in the intervention year with the 2 prior years. Drug desensitizations were assessed by electronic chart review. RESULTS: Most of the patients (n = 656 of 700, 94%) had more than or equal to 1 beta-lactam allergy label removed, clarified, or both; 77.9% of these patients (n = 511 of 656) had 587 beta-lactam allergy labels removed. Nearly one-third (n = 149, 27.6%) had 162 allergy labels removed solely by medication history review. All 114 penicillin skin tests performed had negative results, and 98% (8 of 381) of the patients who underwent any drug challenge passed. Only 5.7% of the delabeled patients were relabeled. There was a 27% reduction in aztreonam use (P = .007). Beta-lactam desensitizations were reduced by 80%. CONCLUSION: A full-time inpatient beta-lactam allergy service using medication history review and risk stratification can safely and effectively remove inpatient beta-lactam allergy labels, reduce aztreonam use, and decrease beta-lactam desensitizations.

Growth failure in focal dermal hypoplasia.

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X chromosome. Short stature was previously noted to be a common finding in FDH, however the etiology of this is unclear. The present study sought to elucidate specific causes for short stature by assessing growth charts, determining bone ages and auxologic measurements, examining laboratory data for the common causes of growth failure, assessing dietary intake, and performing a growth hormone stimulation test. Sixteen patients with FDH between the ages of 3 and 18 years of age consented to the study. While 11 out of 16 patients had short stature based on height less than 2 standard deviations below mid-parental target height percentile and bone age not suggestive of likely catch-up growth, only four had a BMI less than the 5th percentile for age. Laboratory studies did not support a gastrointestinal, allergy or autoimmune cause of growth failure. Three patients had results suggestive of possible growth hormone deficiency. Although short stature is a common feature in FDH, our data suggests that severe undernutrition is not common in this group and that there may be underlying treatable causes for this short stature in some patients.

Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes?

BACKGROUND: Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition. OBJECTIVE: This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. METHODS: Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts. RESULTS: We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups. CONCLUSIONS: Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

French-fried potato consumption and energy balance: a randomized controlled trial.

BACKGROUND: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed. OBJECTIVES: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption. METHODS: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries (potato group), or 3) French fries with herb/spices mix (potato + herb/spices group). Baseline and 30-d FM were measured by DXA (primary outcome), with secondary outcomes including body weight and carbohydrate metabolism markers [glycated hemoglobin (HbA1c), fasting blood glucose and insulin, HOMA-IR)]. A subset of 5 participants/group participated in a postprandial meal-based tolerance test. RESULTS: A total of 180 participants were randomly assigned [gender: 67.8% female; mean ± SD age: 30.4 ± 8.7 y; BMI (in kg/m2): 26.1 ± 4.2; and weight: 75.6 ± 15.4 kg], with 12 dropouts and 3 terminations. No significantly different FM changes were observed between almond and potato consumption [combined ± herb/spices; mean ± SE almond: 230.87 ± 114.01 g; potato: 123.73 ± 86.09 g; P = 0.443], fasting glucose (P = 0.985), insulin (P = 0.082), HOMA-IR (P = 0.080), or HbA1c (P = 0.269). Body weight change was not significantly different in the potato groups combined compared with the almond group (P = 0.116), but was significantly different among the 3 groups (P = 0.014; almond: 0.49 ± 0.20 kg; potato: -0.24 ± 0.20 kg; potato + herb/spices: 0.47 ± 0.21 kg). In meal tests, significantly lower post-prandial glucose and insulin responses to almonds compared with potatoes were observed (P = 0.046, P = 0.006, respectively), with potato + herb/spices having intermediate effects. CONCLUSION: There were no significant differences in FM or in glucoregulatory biomarkers after 30 d of potato consumption compared with almonds. Results do not support a causal relation between increased French fried potato consumption and the negative health outcomes studied. This trial was registered at clinicaltrials.gov as NCT03518515.

The transcription factor c-Myc enhances KIR gene transcription through direct binding to an upstream distal promoter element.

The killer cell immunoglobulin-like receptor (KIR) repertoire of natural killer (NK) cells determines their ability to detect infected or transformed target cells. Although epigenetic mechanisms play a role in KIR gene expression, work in the mouse suggests that other regulatory elements may be involved at specific stages of NK-cell development. Here we report the effects of the transcription factor c-Myc on KIR expression. c-Myc directly binds to, and promotes transcription from, a distal element identified upstream of most KIR genes. Binding of endogenous c-Myc to the distal promoter element is significantly enhanced upon interleukin-15 (IL-15) stimulation in peripheral blood NK cells and correlates with an increase in KIR transcription. In addition, the overexpression of c-Myc during NK-cell development promotes transcription from the distal promoter element and contributes to the overall transcription of multiple KIR genes. Our data demonstrate the significance of the 5' promoter element upstream of the conventional KIR promoter region and support a model whereby IL-15 stimulates c-Myc binding at the distal KIR promoter during NK-cell development to promote KIR transcription. This finding provides a direct link between NK-cell activation signals and KIR expression required for acquisition of effector function during NK-cell education.

Community policing does not build citizen trust in police or reduce crime in the Global South.

Is it possible to reduce crime without exacerbating adversarial relationships between police and citizens? Community policing is a celebrated reform with that aim, which is now adopted on six continents. However, the evidence base is limited, studying reform components in isolation in a limited set of countries, and remaining largely silent on citizen-police trust. We designed six field experiments with Global South police agencies to study locally designed models of community policing using coordinated measures of crime and the attitudes and behaviors of citizens and police. In a preregistered meta-analysis, we found that these interventions led to mixed implementation, largely failed to improve citizen-police relations, and did not reduce crime. Societies may need to implement structural changes first for incremental police reforms such as community policing to succeed.

Anti-integrin monoclonal antibody CNTO 95 enhances the therapeutic efficacy of fractionated radiation therapy in vivo.

Selective targeting of up-regulated integrins on tumor cells is a novel antiangiogenesis strategy for treating solid tumors. CNTO 95 is a fully human anti-alpha(v) integrin monoclonal antibody and has shown antitumor activity when used as a single agent in preclinical studies. We previously showed that radiation combined with an integrin alpha(v)beta(3) antagonist cRGD peptide increased the therapeutic efficacy of radiation in preclinical tumor models. We hypothesized that the combination of radiation and CNTO 95 would synergistically enhance the efficacy of radiation therapy. The in vitro studies showed that CNTO 95 radiosensitized and induced apoptosis in M21 cells in vitronectin-coated dishes. In mice bearing established human cancer xenograft tumors, CNTO 95 alone had only a moderate effect on tumor growth. The combined therapy of CNTO 95 and fractionated radiation significantly inhibited tumor growth and produced the longer tumor growth delay time in multiple tumor models. Maintenance dosing of CNTO 95 following irradiation contributed to efficacy and was important for continued inhibition of tumor regrowth. Immunohistochemistry studies showed that the combined use of CNTO 95 and radiation reduced the alpha(v) integrin and vascular endothelial growth factor receptor expression and the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. CNTO 95 alone and in combination with radiation did not produce any obvious signs of systemic toxicity. These results show that CNTO 95 can potentiate the efficacy of fractionated radiation therapy in a variety of human cancer xenograft tumor types in nude mice. These findings are very promising and may have high translational relevance for the treatment of patients with solid tumors.

Ethnic and Sex Differences in Adiponectin: From Childhood to Adulthood.

CONTEXT: Insulin resistance (IR) and type 2 diabetes are increasing, particularly in Hispanic (H) vs non-Hispanic White (NHW) populations. Adiponectin has a known role in IR, and therefore, understanding ethnic and sex-specific behavior of adiponectin across the lifespan is of clinical significance. OBJECTIVE: To compare ethnic and sex differences in adiponectin, independent of body mass index, across the lifespan and relationship to IR. DESIGN: Cross-sectional. SETTING: Primary care, referral center. PATIENTS: A total of 187 NHW and 117 H participants (8-57 y) without diabetes. Life stage: pre-/early puberty (Tanner 1/2), midpubertal (Tanner 3/4), late pubertal (Tanner 5, <21 years), and adult (Tanner 5, ≥21). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Fasting adiponectin, insulin, glucose, and revised homeostatic model assessment of insulin resistance. RESULTS: Adiponectin was significantly inversely correlated with revised homeostatic model assessment of insulin resistance. Regarding puberty, adiponectin trended downward in late puberty, but only males were significantly lower in adulthood. By sex, adiponectin was lower in adult males vs females of both ethnicities. Regarding ethnicity, H adults of both sexes had lower adiponectin than NHW adults. Of note, in NHW females, adiponectin trended highest in adulthood, whereas in H females, adiponectin fell in late puberty and remained lower in adulthood. CONCLUSIONS: Adiponectin inversely correlated with IR, trended down in late puberty, and was lowest in adult males. H adults of both sexes had lower adiponectin than NHW adults, and H females followed a more "male pattern," lacking the rebound in adiponectin seen in NHW females after puberty. These data suggest that adiponectin, independent of body mass index, may relate to the greater cardiometabolic risk seen in H populations and in particular H females.

Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types.

Using microarray technology, we analyzed 12,000 genes for regulation by TNF-alpha and the synthetic glucocorticoid, dexamethasone, in the human lung epithelial cell line, A549. Only one gene was induced by both agents, the cellular inhibitor of apoptosis 2 (c-IAP2), which was induced 17-fold and 5-fold by TNF-alpha at 2 h and 24 h, respectively, and increased 14-fold and 9-fold by dexamethasone at 2 h and 24 h, respectively. The combination of the two agents together led to an additive increase (34-fold) at 2 h and a more than additive effect (36-fold) at 24 h. The human c-IAP2 promoter contains two nuclear factor (NF)-kappaB sites that have been shown to be required for transcriptional activation by TNF-alpha. To test whether glucocorticoids regulate the c-IAP2 gene at the level of the promoter, a reporter vector containing 947 bases upstream of the start site of transcription of the human c-IAP2 promoter was linked to luciferase [IAP(-947-+54)-LUC] and transfected into A549 cells. Dexamethasone and TNF-alpha each induced reporter activity, whereas the combination of the two agents led to greater induction of luciferase than either one alone. Truncation of the promoter region containing a putative glucocorticoid response element (GRE) at -515 [IAP(-395-+54)-LUC] or mutation of the GRE in the context of the natural promoter [IAP(-947-+54mutGRE)-LUC] resulted in a loss of dexamethasone-mediated induction of reporter activity. Although the functional NF-kappaB sites were retained in the truncated and mutant c-IAP2 promoter constructs, dexamethasone did not inhibit the TNF-alpha induction of luciferase activity, indicating that GR repression through the NF-kappaB sites did not occur. Regulation of the c-IAP2 gene is therefore unique, as GR and NF-kappaB signaling pathways are usually mutually antagonistic, not cooperative. Treatment of A549 cells with TNF-alpha and/or dexamethasone had no effect on cell death, but the two agents were able to inhibit interferon-gamma/anti-FAS antibody-mediated apoptosis. In human glioblastoma A172 cells, TNF-alpha and dexamethasone together elicited a greater than additive increase in c-IAP2 mRNA levels and also inhibited anti-FAS antibody-mediated A172 cell apoptosis. In contrast, in human CEM-C7 leukemic T cells, whereas TNF-alpha and dexamethasone treatment also led to an increase in c-IAP2 mRNA, the two agents were able to induce apoptosis on their own. However, TNF-alpha and dexamethasone were also able to blunt anti-FAS-induced apoptosis in the T cells. These data indicate that the induction of the antiapoptotic protein, c-IAP2, by glucocorticoids and TNF-alpha correlates with the ability of these agents to inhibit apoptosis in a variety of cell types.

Unsuspected or unacknowledged depressive symptoms in young adult emergency department patients.

OBJECTIVES: The objective was to determine the frequency of unsuspected or unacknowledged depressive symptoms among young adult emergency department (ED) patients. METHODS: The Beck Depression Inventory-II (BDI-II) and a demographic/lifestyle questionnaire were administered to a cross-section of medically stable, English-speaking young adult ED patients (aged 18-23 years) with nonpsychiatric chief complaints. The frequency of moderate to severe depressive symptoms was determined. Group results were analyzed with descriptive statistics; multivariate analysis assessed for patient characteristics associated with depressive symptoms. RESULTS: A total of 2,898 patients were screened; 2,255 were eligible for enrollment, and 1,264 enrolled (56%; 64% female, 42% African American; mean age = 21 [+/-1.7] years). Twenty-nine percent had BDI-II scores consistent with moderate to severe depressive symptoms. Patient characteristics associated with depressive symptoms included knowledge of someone who had intentionally hurt him- or herself (odds ratio [OR] = 2) or died a violent nonaccidental death (OR = 1.4), low personal income (OR = 1.8), chronic health issues (OR = 1.7), cigarette smoking (OR = 1.6), and African American race (OR = 1.5). Those who attended school (OR = 0.5), engaged in frequent social activities (OR = 0.5), or drove a car (OR = 0.7) were less likely to have depressive symptoms. Patients lacked insight into their depressive symptoms. CONCLUSIONS: There is a high prevalence of depressive symptoms in young adult ED patients. Young adults often do not recognize, or are reluctant to acknowledge, depressive symptoms. Specific patient characteristics may be useful in deciding which young adults should undergo ED screening for depression.

Communication in young children with motor impairments: teaching caregivers to teach.

Communication between caregivers and children with moderate to severe motor impairments is a tremendous challenge, and one that deserves attention as a central component of early intervention programs. This article examines a caregiver-training program that explored key elements to creating strong communicative interactions between young children with moderate to severe motor impairments and their primary caregiver. Three caregiver-child dyads participated in a 3-week treatment program teaching caregivers how to provide communicative opportunities, wait for a clear communication signal from their children, recognize their children's signal, and finally, shape a more advanced communicative behavior. These adult behaviors were designed to increase the children's use of conventional engaging signals of communication. Results revealed that caregivers demonstrated success learning all behaviors except for shaping during the brief treatment period. Children's engaging communicative behaviors increased correspondingly with the caregivers' changes. These findings have positive implications for caregiver training. Implications for "best practice" are considered.

Depression and anxiety disorders in pediatric epilepsy.

PURPOSE: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure-related, cognitive, linguistic, family history, social competence, and demographic variables. METHODS: A structured psychiatric interview, mood self-report scales, as well as cognitive and language testing were administered to 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral information on each child through a structured psychiatric interview and behavior checklist. RESULTS: Significantly more patients had affective and anxiety disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal group, but none had made a suicide attempt. Anxiety disorder was the most frequent diagnosis among the patients with a diagnosis of affective or anxiety disorders, and combined affective/anxiety and disruptive disorder diagnoses, in those with suicidal ideation. Only 33% received some form of mental health service. Age, verbal IQ, school problems, and seizure type were related to the presence of a diagnosis of affective or anxiety disorder, and duration of illness, to suicidal ideation. CONCLUSIONS: These findings together with the high rate of unmet mental health underscore the importance of early detection and treatment of anxiety disorders and suicidal ideation children with CPSs and CAE.