Prescribing patterns in patients with obsessive-compulsive disorder: Retrospective, single-center study.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States. METHODS: This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety-five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM-5 criteria. RESULTS: Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second-generation antipsychotics (37%). Tricyclic antidepressants and first-generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin-norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively. CONCLUSIONS: Evidence-based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first-line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.

Erratum: Ascofuranone antibiotic is a promising trypanocidal drug for nagana.

No abstract available.

The Effect of Diesel Exhaust Particles on Adipose Tissue Mitochondrial Function and Inflammatory Status.

Air pollution poses a significant global health risk, with fine particulate matter (PM2.5) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM2.5 exposure and an increased prevalence of metabolic disorders, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), is evident against a backdrop of rising global obesity and poor metabolic health. This paper examines the role of adipose tissue in mediating the effects of PM2.5 on metabolic health. Adipose tissue, beyond its energy storage function, is responsive to inhaled noxious stimuli, thus disrupting metabolic homeostasis and responding to particulate exposure with pro-inflammatory cytokine release, contributing to systemic inflammation. The purpose of this study was to characterize the metabolic response of adipose tissue in mice exposed to either DEPs or room air (RA), exploring both the adipokine profile and mitochondrial bioenergetics. In addition to a slight change in fat mass and a robust shift in adipocyte hypertrophy in the DEP-exposed animals, we found significant changes in adipose mitochondrial bioenergetics. Furthermore, the DEP-exposed animals had a significantly higher expression of adipose inflammatory markers compared with the adipose from RA-exposed mice. Despite the nearly exclusive focus on dietary factors in an effort to better understand metabolic health, these results highlight the novel role of environmental factors that may contribute to the growing global burden of poor metabolic health.

Ascofuranone antibiotic is a promising trypanocidal drug for nagana.

Trypanosomosis is a disease complex which affects both humans and animals in sub-Saharan Africa, transmitted by the tsetse fly and distributed within the tsetse belt of Africa. But some trypanosome species, for example, Trypanosoma brucei evansi, T. vivax, T. theileri and T. b. equiperdum are endemic outside the tsetse belt of Africa transmitted by biting flies, for example, Tabanus and Stomoxys, or venereal transmission, respectively. Trypanocidal drugs remain the principal method of animal trypanosomosis control in most African countries. However, there is a growing concern that their effectiveness may be severely curtailed by widespread drug resistance. A minimum number of six male cattle calves were recruited for the study. They were randomly grouped into two (T. vivax and T. congolense groups) of three calves each. One calf per group served as a control while two calves were treatment group. They were inoculated with 105 cells/mL parasites in phosphate buffered solution (PBS) in 2 mL. When parasitaemia reached 1 × 107.8 cells/mL trypanosomes per mL in calves, treatment was instituted with 20 mL (25 mg/kg in 100 kg calf) ascofuranone (AF) for treatment calves, while the control ones were administered a placebo (20 mL PBS) intramuscularly. This study revealed that T. vivax was successfully cleared by AF but the T. congolense group was not cleared effectively.Contribution: There is an urgent need to develop new drugs which this study sought to address. It is suggested that the AF compound can be developed further to be a sanative drug for T. vivax in non-tsetse infested areas like South Americas.

The effect of parent-adolescent discrepancies in reports of familial dysfunction and depression on suicidal ideation in adolescents.

INTRODUCTION: Parents and adolescents are often discrepant in their reports of adolescent psychosocial factors. Few studies have addressed parent-adolescent discrepancies in subjective ratings of familial dysfunction and depression as longitudinal predictor variables, and none have done so in a treatment setting for adolescents with acute suicidality. This study examined how parent-adolescent discrepancies in familial dysfunction and depression impact adolescent treatment response in an intensive outpatient program for suicidality. METHODS: Adolescents (N = 315) were assessed at treatment entry and exit for familial dysfunction, depression, and suicidal ideation. Parents received parallel assessments of familial dysfunction and adolescent depression at each time point. A polynomial regression was conducted to determine whether parent-adolescent discrepancies in reports of familial dysfunction and depression at entry related to the treatment outcome of adolescent-reported depression and suicide ideation at exit. RESULTS: Significant discrepancies were present with on average adolescents reporting more depression and familial dysfunction than parents. Entry discrepancy in familial dysfunction (but not depression) predicted suicide ideation at exit. CONCLUSIONS: Our results suggest that parent-adolescent discrepancies in perception of familial dysfunction is a risk factor for poor outcomes in suicidal youth and might be a fruitful target in treatment programs.

The association between Superwoman schema and subjective sleep quality among Black women.

OBJECTIVES: Similar to women overall, Black women are socialized to be communal and "self-sacrificing," but unlike women from other racial/ethnic backgrounds, Black women are also socialized to be "strong" and "invulnerable." This phenomenon is labeled Superwoman schema. This study examined associations between Superwoman schema endorsement and subjective sleep quality. METHODS: Participants included 405 Black women (ages 30-46). Superwoman schema was measured using a 35-item scale capturing five dimensions: obligation to present strength, suppress emotions, resistance to vulnerability, motivation to succeed, and obligation to help others. Superwoman schema overall and the five dimensions/subscales were analyzed. The Pittsburgh Sleep Quality Index (PSQI) was used to investigate overall subjective sleep quality (range: 0-19), poor sleep quality (PSQI >5), and specific sleep domains (eg, sleep duration, sleep disturbances). We fit linear and binary logistic regression models, adjusting for health-related and sociodemographic factors. RESULTS: Superwoman schema dimension obligation to help others was associated with lower overall subjective sleep quality (ß: .81, 95%CI=0.29, 1.32) and poor sleep quality (OR: 1.55, 95%CI=1.10, 2.19), as well as bad subjective sleep quality (OR: 1.76, 95%CI=1.18, 2.66), sleep disturbances (ß: .73, 95%CI =0.07, 1.41), and daytime sleepiness (OR: 2.01, 95%CI=1.25, 3.26). Suppress emotions (OR: 1.41, 95%CI=1.01, 1.99) was associated with poor subjective sleep quality. Superwoman schema overall was associated with daytime sleepiness (OR: 2.01, 95%CI=1.06, 3.82). CONCLUSION: Superwoman schema endorsement, especially obligation to help others and suppress emotions, may be important psychosocial risk factors for Black women's sleep health.

Antibody-Dependent Respiratory Burst against Plasmodium falciparum Merozoites in Individuals Living in an Area with Declining Malaria Transmission.

Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate measure of protection against malaria is lacking. However, antibody-mediated functions against Plasmodium falciparum correlate with protection against malaria. In children, antibody-mediated functions against P. falciparum decline with reduced exposure. It is unclear whether adults maintain antibody-mediated functions as malaria transmission declines. This study assessed antibody-dependent respiratory burst (ADRB) in individuals from an area with declining malaria transmission. In an age-matched analysis, we compare ADRB activity during high versus low malaria transmission periods. Age significantly predicted higher ADRB activity in the high (p < 0.001) and low (p < 0.001) malaria transmission periods. ADRB activity was higher during the high compared to the low malaria transmission period in older children and adults. Only older adults during the high malaria transmission period had their median ADRB activity above the ADRB cut-off. Ongoing P. falciparum infection influenced ADRB activity during the low (p = 0.01) but not the high (p = 0.29) malaria transmission period. These findings propose that naturally acquired immunity to P. falciparum is affected in children and adults as malaria transmission declines, implying that vaccines will be necessary to induce and maintain protection against malaria.

Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

BACKGROUND: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. METHODS: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. RESULTS: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. CONCLUSIONS: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): Aortic stiffness & intracranial atherosclerosis.

OBJECTIVES: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20  % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. RESULTS: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. CONCLUSIONS: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.

Negative Mood Dysregulation Loads Strongly Onto Common Factors With Many Forms of Psychopathology: Considerations for Assessing Nonspecific Symptoms.

There have been proposals to expand definitions for categorical disorders and dimensionally conceptualized syndromes (e.g., psychopathy) to include negative mood lability and dysregulation (NMD). Factor analytic results are often presented in support of these proposals, and we provide factor analytic demonstrations across clinically oriented samples showing that NMD indicators load strongly onto factors with a range of psychopathology. This is unsurprising from a transdiagnostic perspective but shows that factor analysis could potentially be used to justify expanding definitions for specific constructs even though NMD indicators show strong, nonspecific loadings on psychopathology factors ranging widely in nature. Expanding construct definitions and assessment approaches to emphasize NMD also may negatively impact discriminant validity. We agree that targeting NMD is essential for comprehensive assessment, but our demonstrative analyses highlight a need for using factor analysis and other statistical methods in a careful, theoretically driven manner when evaluating psychopathology structure and developing measures.

Awareness of Narrative Identity Questionnaire (ANIQ) in Early Adolescents: Psychometric Evaluation and Association with Features of Personality Disorder.

Identity formation is central to adolescent development. Challenges in establishing a stable sense of self is associated with maladaptive identity function, which has been recognized as a core feature of personality pathology. The narrative identity framework offers a unique lens to garner salient information about one's sense of self. The Awareness of Narrative Identity Questionnaire (ANIQ) is a self-report measure of narrative identity validated in adults but is yet to be validated in adolescents. The current study aimed to conduct the first psychometric evaluation of the ANIQ in a sample of 205 youth aged 10-14 years (M = 12.1 ± 1.06 years; 50.7% female; 73.7% Hispanic) recruited from a public charter school. Results confirmed the four-factor structure of the ANIQ and showed high internal consistency. Convergent validity was supported through negative associations between the ANIQ and borderline personality features and identity diffusion. Incremental validity of the ANIQ over identity diffusion in predicting borderline personality features was also examined, but not supported. Overall, results support the ANIQ as a promising instrument for the assessment of narrative identity in youth. However, some improvements to the ANIQ might be necessary in order to use it as a clinical tool in identifying youth with personality pathology.

Predicting methane emissions of individual grazing dairy cows from spectral analyses of their milk samples.

Data on the enteric methane emissions of individual cows are useful not just in assisting management decisions and calculating herd inventories but also as inputs for animal genetic evaluations. Data generation for many animal characteristics, including enteric methane emissions, can be expensive and time consuming, so being able to extract as much information as possible from available samples or data sources is worthy of investigation. The objective of the present study was to attempt to predict individual cow methane emissions from the information contained within milk samples, specifically the spectrum of light transmittance across different wavelengths of the mid-infrared (MIR) region of the electromagnetic spectrum. A total of 93,888 individual spot measures of methane (i.e., individual samples of an animal's breath when using the GreenFeed technology) from 384 lactations on 277 grazing dairy cows were collapsed into weekly averages expressed as grams per day; each weekly average coincided with a MIR spectral analysis of a morning or evening individual cow milk sample. Associations between the spectra and enteric methane measures were performed separately using partial least squares regression or neural networks with different tuning parameters evaluated. Several alternative definitions of the enteric methane phenotype (i.e., average enteric methane in the 6 d preceding or 6 d following taking the milk sample or the average of the 6 d before and after the milk sample, all of which also included the enteric methane emitted on the day of milk sampling), the candidate model features (e.g., milk yield, milk composition, and milk MIR) as well as validation strategy (i.e., cross-validation or leave-one-experimental treatment-out) were evaluated. Irrespective of the validation method, the prediction accuracy was best when the average of the milk MIR from the morning and evening milk sample was used and the prediction model was developed using neural networks; concurrently including milk yield and days in milk in the prediction model generated superior predictions relative to just the spectral information alone. Furthermore, prediction accuracy was best when the enteric methane phenotype was the average of at least 20 methane spot measures across a 6-d period flanking each side of the milk sample with associated spectral data. Based on the strategy that achieved the best accuracy of prediction, the correlation between the actual and predicted daily methane emissions when based on 4-fold cross-validation varied per validation stratum from 0.68 to 0.75; the corresponding range when validated on each of the 8 different experimental treatments focusing on alternative pasture grazing systems represented in the dataset varied from 0.55 to 0.71. The root mean square error of prediction across the 4-folds of cross-validation was 37.46 g/d, whereas the root mean square error averaged across all folds of leave-one-treatment-out was 37.50 g/d. Results suggest that even with the likely measurement errors contained within the MIR spectrum and gold standard enteric methane phenotype, enteric methane can be reasonably well predicted from the infrared spectrum of milk samples. What is yet to be established, however, is whether (a) genetic variation exists in this predicted enteric methane phenotype and (b) selection on estimates of genetic merit for this phenotype translate to actual phenotypic differences in enteric methane emissions.

Feasibility Randomised Control Trial of OptiMal: A Self-Management Intervention for Cancer Survivors.

PURPOSE: Cancer survivors can experience symptoms such as fatigue, pain and distress that persist for many months following treatment. These enduring symptoms often impact on participation in self-care activities, returning to school and/or work, and leisure and social activities. Self-management support is increasingly recognised as a core aspect of cancer survivorship care to reduce the impact of persistent symptoms. The purpose of this study was to examine the feasibility and potential effectiveness of a group-based self-management intervention, OptiMal, to improve the physical and psychological health of cancer survivors. OptiMal is a six-week intervention comprising weekly sessions on fatigue, stress and physical activity, diet and effective communication strategies. METHODS: A feasibility randomised control trial was undertaken. Individuals up to two years after cancer treatment were randomised to OptiMal or usual care. Feasibility was examined through recruitment and retention metrics. Potential effectiveness was tested through patient-reported outcomes collected at baseline and three months post-intervention. Descriptive and inferential statistics were used to analyse study data. RESULTS: Recruitment for this study was 32.5% (80/246 eligible individuals) with 77.5% retention at three-month follow-up (82.5% for intervention group and 72.5% for control group). Of those who attended the intervention, 19 (73%) attended all OptiMal sessions, indicating high adherence to the intervention. The majority of participants had breast cancer and were between 12 and 24 months post-treatment. The intervention group (n = 29) had statistically significant greater improvements in anxiety (p = 0.04) and health-related quality of life (health index score: p = 0.023, visual analogue score: p = 0.035) at three months post-intervention than the control group. CONCLUSIONS: Recruitment and retention in this study was similar to other cancer trials and the high adherence rate indicates that OptiMal is an acceptable self-management intervention for cancer survivors and warrants further investigation. OptiMal is intended to address symptoms reported across different cancer types. However, a limitation of this study was that the majority of participants had breast cancer, and therefore, generalisability of findings cannot be assumed for other cancer types. Future studies of OptiMal therefore need to use different strategies to recruit survivors of other cancer types.

Feasibility of a pragmatic randomized adaptive clinical trial to evaluate a brief negotiational interview for harmful and hazardous alcohol use in Moshi, Tanzania.

INTRODUCTION: Low-resourced settings often lack personnel and infrastructure for alcohol use disorder treatment. We culturally adapted a Brief Negotiational Interview (BNI) for Emergency Department injury patients, the "Punguza Pombe Kwa Afya Yako (PPKAY)" ("Reduce Alcohol For Your Health") in Tanzania. This study aimed to evaluate the feasibility of a pragmatic randomized adaptive controlled trial of the PPKAY intervention. MATERIALS AND METHODS: This feasibility trial piloted a single-blind, parallel, adaptive, and multi-stage, block-randomized controlled trial, which will subsequently be used to determine the most effective intervention, with or without text message booster, to reduce alcohol use among injury patients. We reported our feasibility pilot study using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, with recruitment and retention rates being our primary and secondary outcomes. We enrolled adult patients seeking care for an acute injury at the Kilimanjaro Christian Medical Center in Tanzania if they (1) exhibited an Alcohol Use Disorder Identification Test (AUDIT) ≥8, (2) disclosed alcohol use prior to injury, or (3) had a breathalyzer ≥0.0 on arrival. Intervention arms were usual care (UC), PPKAY, PPKAY with standard text booster, or a PPKAY with a personalized text booster. RESULTS: Overall, 181 patients were screened and 75 enrolled with 80% 6-week, 82.7% 3-month and 84% 6-month follow-up rates showing appropriate Reach and retention. Adoption measures showed an overwhelmingly positive patient acceptance with 100% of patients perceiving a positive impact on their behavior. The Implementation and trial processes were performed with high rates of PPKAY fidelity (76%) and SMS delivery (74%). Intervention nurses believed Maintenance and sustainability of this 30-minute, low-cost intervention and adaptive clinical trial were feasible. CONCLUSIONS: Our intervention and trial design are feasible and acceptable, have evidence of good fidelity, and did not show problematic deviations in protocol. Results suggest support for undertaking a full trial to evaluate the effectiveness of the PPKAY, a nurse-driven BNI in a low-income country. TRIAL REGISTRATION: Trial registration number NCT02828267. https://classic.clinicaltrials.gov/ct2/show/NCT02828267.

Induction of glucose production by heterocyclic amines is dependent on N-acetyltransferase 2 genetic polymorphism in cryopreserved human hepatocytes.

Heterocyclic amines (HCAs) are mutagenic compounds found in cooked meat. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes, and we recently reported that HCAs induce insulin resistance and glucose production in human hepatocytes. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlates to rapid, intermediate, or slow acetylator phenotype that exhibits differential metabolism of aromatic amines and HCAs. No previous studies have examined the role of NAT2 genetic polymorphism in the context of HCA-mediated induction of glucose production. In the present study, we assessed the effect of three HCAs commonly found in cooked meat (2-amino-3,4-dimethylimidazo[4,5-f]quinoline [MeIQ], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP]) on glucose production in cryopreserved human hepatocytes with slow, intermediate, or rapid NAT2 acetylator phenotype. HCA treatment did not affect glucose production in slow NAT2 acetylator hepatocytes, while a slight increase in glucose production was observed in intermediate NAT2 acetylators treated with MeIQ or MeIQx. However, significant increases in glucose production were observed in rapid NAT2 acetylators following each HCA. The current findings suggest that individuals who are rapid NAT2 acetylators may be at a greater risk of developing hyperglycemia and insulin resistance following dietary exposure to HCAs.

Decreased Expression of Pulmonary Homeobox NKX2.1 and Surfactant Protein C in Developing Lungs That Over-Express Receptors for Advanced Glycation End-Products (RAGE).

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin superfamily prominently expressed by lung epithelium. Previous experiments demonstrated that over-expression of RAGE by murine alveolar epithelium throughout embryonic development causes neonatal lethality coincident with significant lung hypoplasia. In the current study, we evaluated the expression of NKX2.1 (also referred to as TTF-1), a homeodomain-containing transcription factor critical for branching morphogenesis, in mice that differentially expressed RAGE. We also contextualized NKX2.1 expression with the abundance of FoxA2, a winged double helix DNA binding protein that influences respiratory epithelial cell differentiation and surfactant protein expression. Conditional RAGE over-expression was induced in mouse lung throughout gestation (embryonic day E0-18.5), as well as during the critical saccular period of development (E15.5-18.5), and analyses were conducted at E18.5. Histology revealed markedly less lung parenchyma beginning in the canalicular stage of lung development and continuing throughout the saccular period. We discovered consistently decreased expression of both NKX2.1 and FoxA2 in lungs from transgenic (TG) mice compared to littermate controls. We also observed diminished surfactant protein C in TG mice, suggesting possible hindered differentiation and/or proliferation of alveolar epithelial cells under the genetic control of these two critical transcription factors. These results demonstrate that RAGE must be specifically regulated during lung formation. Perturbation of epithelial cell differentiation culminating in respiratory distress and perinatal lethality may coincide with elevated RAGE expression in the lung parenchyma.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Implementation of E-Consults in an Integrated Health System for a Value Population.

The adoption of e-consults, a form of formal, asynchronous provider-to-provider communication in which specialty medical advice is sought, has been proven to reduce unnecessary specialty consultations, build provider relationships, and reduce fragmentation of care. While the utilization of e-consults is generally a well-accepted alternative method of incorporating specialist expertise into a patient's plan of care and adoption has become common, the implementation of this disruptive care delivery modality can be challenging. This article seeks to describe the process and operational outcomes of e-consult adoption in an integrated health system with a focus on the benefits in the context of value-based care. Implications of e-consult adoption on referral volumes, wait times, and cancellation rates at the service line level are investigated. E-consult adoption and completion metrics, including utilization, completed versus rejected, turn-around times, and projected cost savings, are also discussed.