Nimodipine-associated standard dose reductions and neurologic outcomes after aneurysmal subarachnoid hemorrhage: the era of pharmacogenomics.

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.

Infectious Extensor Tenosynovitis of the Hallucis Longus Tendon: A Case Report.

Infectious tenosynovitis can involve both flexor and extensor tendons of the extremities. If left untreated, it can lead to high morbidity and mortality. Most emergency providers recognize the signs and symptoms of flexor and extensor tenosynovitis of the hand. However, extensor tenosynovitis of the hallucis longus tendon is a rare condition with a risk of complications similar to infectious tenosynovitis of the hand. This case report describes a presentation of extensor tenosynovitis of the hallucis longus tendon. Clinical suspicion is essential to help the provider not miss this rare condition, which can lead to significant morbidity if not treated promptly or appropriately.

Testing a Pediatric Palliative Care Education Workplace Intervention.

Pediatric palliative care is aimed at pain and symptom management, reducing hospitalization, promoting psychosocial care, and improving quality of life for children with serious illness. As a professional caregiver, nurses play an essential role in the provision of appropriate pediatric palliative care in clinical care settings. The purpose of this quality improvement study was to improve pediatric nurses' awareness and perceptions of palliative care. A 1-group pretest-posttest design was used in the study. A 20-minute education video was used as an intervention to enhance nurses' awareness and perception about pediatric palliative care. Twenty-one pediatric medical-surgical nurses participated in the intervention. Posttest results indicated raised awareness about palliative care, more nurses were able to define palliative care correctly, and nurses were more likely to encourage a palliative care consult. Future studies are needed using larger sample sizes with robust measures to further evaluate the effectiveness of the intervention on enhancing pediatric palliative care awareness among nurses.

Surfeit folic acid, protein, and exercise modify oncogenic inflammatory biomarkers and fecal microbiota.

Intestinal microbiota, diet, and physical activity are inextricably linked to inflammation occurring in the presence of tumor progression and declining neurocognition. This study aimed to explore how fecal microbiota, inflammatory biomarkers, and neurocognitive behavior are influenced by voluntary exercise and surplus dietary protein and folic acid which are common health choices. Dietary treatments provided over 8 weeks to C57BL/CJ male mice (N = 76) were: Folic Acid (FA) Protein (P) Control (FPC, 17.9% P; 2 mgFA/kg); Folic Acid Deficient (FAD); Folic Acid Supplemented (FAS; 8 mgFA/kg); Low Protein Diet (LPD, 6% P); and High Protein Diet (HPD, 48% P). FAS mice had decreased plasma HCys (p < 0.05), therefore confirming consumption of FA. Objectives included examining influence of exercise using Voluntary Wheel Running (VWR) upon fecal microbiota, inflammatory biomarkers C - reactive protein (CRP), Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), nuclear factor kappa ß subunit (NF-κßp65), Caspase-3 (CASP3), Tumor Necrosis Factor-alpha (TNF-α), and neurocognitive behavior. CRP remained stable, while a significant exercise and dietary effect was notable with decreased VEGF (p < 0.05) and increased CASP3 (p < 0.05) for exercised HPD mice. Consumption of FAS did significantly increase (p < 0.05) muscle TNF-α and the ability to build a nest (p < 0.05) was significantly decreased for both FAD and LPD exercised mice. Rearing behavior was significantly increased (p < 0.05) in mice fed HPD. An emerging pattern with increased dietary protein intake revealed more distance explored in Open Field Testing. At week 1, both weighted and unweighted UniFrac principal coordinates analysis yielded significant clustering (permanova, p ≤ 0.05) associated with the specific diets. Consumption of a HPD diet resulted in the most distinct fecal microbiota composition. At the phylum level-comparing week 1 to week 8-we report a general increase in the Firmicutes/Bacteroidetes ratio, characterized by an outgrowth of Firmicutes by week 8 in all groups except the HPD. MaAsLin2 analysis corroborates this finding and emphasizes an apparent inversion of the microbiome composition at week 8 after HPD. Explicit modification of oncogenic inflammatory biomarkers and fecal microbiome post high FA and protein intake along with voluntary exercise contributed to current underlying evidence that this diet and exercise relationship has broader effects on human health and disease-perhaps importantly as a practical modulation of cancer progression and declining neurocognition.

Nimodipine-induced junctional bradycardia in an elderly patient with subarachnoid hemorrhage.

Subarachnoid hemorrhage is a devastating form of stroke with often detrimental outcomes for patients. Here we describe a patient with subarachnoid hemorrhage treated with nimodipine, which resulted in marked bradycardia with junctional atrioventricular heart block. Nimodipine is metabolized predominantly by the cytochrome P450 3A subfamily, and its use is often associated with adverse events, such as hypotension and bradycardia, which can be exacerbated by advanced age. Our patient had the CYP3A5*3/*3 genotype, possibly predisposing her to poor metabolism of this drug. Our case report demonstrates the potential for pharmacogenomics in patients with subarachnoid hemorrhage to help predict their response to nimodipine, minimize adverse drug reactions, and potentially individualize dosing to improve future clinical outcomes.

Pharmacogenomics of Cytochrome P450 of Nimodipine Metabolism After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke that is life threatening with high rates of mortality, and many survivors are left with permanent neurologic deficits. Nimodipine is the treatment of choice for aSAH with the goal of reduction of delayed cerebral ischemia. It is the only evidence-based medication that has been shown to have improved outcomes for delayed cerebral ischemia; therefore, it is important for neuroscience nurses to be knowledgeable of the pharmacology and pharmacogenomics properties of this medication, including cytochrome P450 (CYP450) enzymes. METHODS AND RESULTS: This article reviews the CYP450 enzyme system including a review of the pharmacotherapy and pharmacogenomics of nimodipine for patients with aSAH illustrated with case study of a patient with abnormal drug metabolism. CONCLUSION: CYP450 enzymes can be inhibited or induced by multiple medications resulting in clinically significant differences in drug metabolism. Food and Drug Administration-approved medication nimodipine is the only medication shown to improve outcomes in patients with aSAH. Hence, it is important to have awareness of potential drug-to-drug interactions and pharmacogenomics of nimodipine when caring for critically ill patients with aSAH.

Assessing the Linkage between Exposure to Violence and Victimization, Coping, and Adjustment among Urban Youth: Findings from a Research Study on Adolescents.

From examinations of the literature on the influence that exposure to violence and coping strategies have on delinquent behavior and emotional outcomes, this study addresses the association between violent victimization and the moderating effects of coping strategies among 500 African-American adolescents who exhibit both externalizing behaviors such as delinquency and internalizing symptoms, including anxiety and depression. The investigation examines the development of the aforementioned adjustment problems in response to victimization, and the findings indicate a relationship between the specific indices of victimization, including peer violence, and the symptomatology and coping mechanisms utilized by the youth in this study. Suggestions for future research in this area are discussed.

Health Care Disparities Knowledge, Attitudes, and Behaviors in Resident Physicians.

PURPOSE: Health care disparities are an important but sometimes underrepresented topic in graduate medical education. In this study we measured the impact of educational and behavioral interventions on resident knowledge about and attitudes toward health care disparities. METHODS: Faculty from 6 residency programs designed and presented an hour-long educational intervention to emphasize the importance of and increase resident knowledge about health care disparities. Selected residents then helped design a month-long behavioral intervention to engage their peers in conversations about disparities with patients. Surveys were administered pre- and post-educational intervention as well as post-behavioral intervention in order to measure the impact each intervention had on resident knowledge and attitudes. RESULTS: Paired-samples t-tests showed that residents were more knowledgeable about health care disparities issues following didactic teaching (P<0.001) and felt such issues were more important (P<0.001). Furthermore, presence of these feelings significantly predicted the frequency of engaging in the behavioral intervention (r=0.44, P<0.01). CONCLUSIONS: Two brief, simple interventions produced significant changes in resident knowledge, attitudes and behaviors regarding health care disparities. The educational intervention was most effective at increasing knowledge of disparities in general and encouraging participation in the behavioral intervention, while the behavioral intervention was useful in increasing knowledge of specific patients' barriers to care.

The risks of partner violence following HIV status disclosure, and health service responses: narratives of women attending reproductive health services in Kenya.

INTRODUCTION: For many women living with HIV (WLWH), the disclosure of positive status can lead to either an extension of former violence or new conflict specifically associated with HIV status disclosure. This study aims to explore the following about WLWH: 1. the women's experiences of intimate partner violence (IPV) risks following disclosure to their partners; 2. an analysis of the women's views on the role of health providers in preventing and addressing IPV, especially following HIV disclosure. METHODS: Thirty qualitative interviews were conducted with purposively selected WLWH attending clinics in Kenya. Data were coded using NVivo 9 and analyzed thematically. RESULTS: Nearly one third of the respondents reported experiencing physical and/or emotional violence inflicted by their partners following the sero-disclosure, suggesting that HIV status disclosure can be a period of heightened risk for partner stigma and abuse, and financial withdrawal, and thus should be handled with caution. Sero-concordance was protective for emotional and verbal abuse once the partner knew his positive status, or knew the woman knew his status. Our results show acceptance of the role of the health services in helping prevent and reduce anticipated fear of partner stigma and violence as barriers to HIV disclosure. Some of the approaches suggested by our respondents included couple counselling, separate counselling sessions for men, and facilitated disclosure. The women's narratives illustrate the importance of integrating discussions on risks for partner violence and fear of disclosure into HIV counselling and testing, helping women develop communication skills in how to disclose their status, and reducing fear about marital separation and break-up. Women in our study also confirmed the key role of preventive health services in reducing blame for HIV transmission and raising awareness on HIV as a chronic disease. However, several women reported receiving no counselling on safe disclosure of HIV status. CONCLUSION: Integration of partner violence identification and care into sexual, reproductive and HIV services for WLWH could be a way forward. The health sector can play a preventive role by sensitizing providers to the potential risks for partner violence following disclosure and ensuring that the women's decision to disclose is fully informed and voluntary.

A microprocessor-controlled tracheal insufflation-assisted total liquid ventilation system.

A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures. The system can also provide a unique continuous perfusion (bias flow, tracheal insufflation) through one lumen of a double-lumen endotracheal catheter to increase washout of dead space liquid. FRC and arterial blood gases were maintained during ventilation with Rimar 101 PFC over 2-3 h in normal piglets and piglets with simulated pulmonary edema induced by instillation of albumin solution. Addition of tracheal insufflation flow significantly improved the blood gases and enhanced clearance of instilled albumin solution during simulated edema.