Pulsed ion deflection to overcome detector saturation in cryogenic ice sampling.

In 2014, we introduced a new experimental approach to study the UV photo-processing of cryogenic ices of astrophysical interest using laser ablation in a combination of ionization and time-of-flight mass spectrometry (ToF-MS). The setup, Mass Analytical Tool to Research Interstellar ICES, allowed us to detect newly formed species at low abundances. However, we found that with the increase in molecular complexity over the years, the detection of larger photoproducts was hindered by the dynamic range of detectors used. Here, we introduce a method to overcome this issue that we expect to be useful for similar applications in other research fields. The concept is based on a precisely controlled high-energy pulser that regulates the voltage across the deflection plates of the ToF-MS instrument to deflect the most abundant species and prevent them from reaching the detector. In this way, the detector sensitivity can be increased from an operating voltage of 2500 V up to 3000 V. The applicability is first illustrated in the simple case of an argon matrix, where 40Ar+ ions are deflected to increase the detection sensitivity for 40Ar2+ at m/z = 20 and 40Ar2+ at m/z = 80 by a factor 30. Similarly, it is shown that substantially larger complex organic molecules, an important species in astrochemical reaction networks, can be measured for UV irradiated methanol ice.

Perioperative Anticoagulation in Patients with Cancer.

PURPOSE OF REVIEW: There is a paucity of evidence for managing perioperative anticoagulation in patients with cancer. This review aims to provide clinicians who provide care for patients with cancer an overview of the available information and strategies needed to provide optimal care in a perioperative setting. RECENT FINDINGS: There is new evidence available around the management of perioperative anticoagulation in patients with cancer. The new literature and guidance were analyzed and summarized in this review. Management of perioperative anticoagulation in individuals with cancer is a challenging clinical dilemma. The approach to managing anticoagulation requires clinicians to review both disease and treatment specific patient factors that can contribute to both thrombotic and bleed risks. A thorough patient-specific assessment is essential in ensuring patients with cancer receive appropriate care in the perioperative setting.

Ideal Foundational Requirements for Stroke Program Development and Growth: A Scientific Statement From the American Heart Association.

Stroke center certification has evolved at a rapid pace and is now available at 4 different levels of service in the United States. Although certification standards provide guidance on stroke center process elements, lack of guidance on structural components such as workforce, staffing, and unit operations has resulted in heterogeneous services among hospitals credentialed at the same stroke center level. Such heterogeneity challenges public expectations and transparency about actual service capabilities within American stroke centers and in some cases may foster leniency in credentialing agency certification methods. Standards for other time-dependent diagnoses, including trauma, provide detailed guidance on structural elements that has improved patient triage and resuscitative care while enabling practitioners and administrators to more accurately gauge and plan service development to better support their communities. This scientific statement aims to provide similar structural guidance defined by each level of hospital stroke center services to reduce operational inconsistencies, to foster planning for service development, and to improve the interprofessional care of patients with acute stroke.

Perioperative Anticoagulation Management.

Management of anticoagulation in individuals undergoing operative procedures is a complex situation. Each case should be assessed individually with proper risk assessment, monitoring, and plan for perioperative and postoperative anticoagulation. Clinical evidence for the management of these patients is relatively scarce, and clinicians are often assessing each individual case with minimal guidance. This review provides nurses with a summary of available literature on the assessment, laboratory monitoring, timing of adjusting anticoagulation, and bridging prior to procedures. In addition to general perioperative anticoagulation management, this review discusses perioperative management in special populations and provides a summary on principles when anticoagulation should be resumed following a procedure.

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are a new class of heart failure medications that have previously been exclusively utilized in the management of type 2 diabetes mellitus (T2DM). The rationale for using SGLT-2 inhibitors in patients with heart failure has stemmed from recent landmark clinical trials in T2DM in which reductions in mortality and hospitalization for heart failure were first observed. On the basis of these robust outcomes, empagliflozin has further been evaluated in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction and dapagliflozin solely in the management of HFrEF. While cardiovascular outcomes among each agent vary depending on the patient population, updates among both the American and European guidelines have included SGLT-2 inhibitors as pillars of therapy. The exact mechanisms for how SGLT-2 inhibitors are beneficial in heart failure are unknown, but current hypotheses include multiple metabolic and hemodynamic mechanisms. The purpose of this review is to summarize available literature focusing on the use of the SGLT-2 inhibitors as adjunctive therapy in heart failure, as well as evaluate mechanisms for heart failure benefit, adverse effects, and practical considerations for using these agents in the clinical setting.

Fenfluramine for seizures associated with Sunflower syndrome.

AIM: To determine the efficacy of fenfluramine on seizure frequency in patients with Sunflower syndrome. Secondary endpoints were changes in electroencephalogram (EEG) characteristics, cognitive functioning, executive functioning, and quality of life. METHOD: In this open-label study, patients underwent a 4-week baseline period, followed by 3 months of treatment. An oral solution of fenfluramine was administered twice daily for 3 months. The dose was titrated up to a maximum dose of 0.7mg/kg/day or 26mg/day. Cardiac safety was monitored by transthoracic echocardiogram and electrocardiogram. EEGs, abbreviated neuropsychological testing, and questionnaires were administered before starting the study medication and again at the end of the treatment period. RESULTS: Ten patients (eight females, two males; mean age 13y 4mo [SD 4y 11mo], range 7-24y) were enrolled in the study. Nine of the 10 patients completed the core study, eight of whom met the primary endpoint. There were no observations of cardiac valvulopathy or pulmonary hypertension during the study. INTERPRETATION: Treatment with low-dose fenfluramine resulted in a clinically significant reduction in seizure frequency, including hand-waving episodes. Fenfluramine may be an effective treatment option for patients with Sunflower syndrome. What this paper adds Nine patients with Sunflower syndrome were treated with fenfluramine. Eight patients were responders, displaying a ≥30% reduction in seizure activity. Six patients experienced a ≥70% reduction in hand-waving episodes. Improvements on electroencephalogram were observed after treatment with fenfluramine. None of the patients developed evidence of cardiac valvulopathy or pulmonary hypertension.

Understanding Sunflower syndrome: Results of an online questionnaire.

OBJECTIVE: To characterize the clinical phenotype, treatments, and impact on quality of life of Sunflower syndrome. METHODS: A 138-question survey was created focusing on seizure description, disease course, treatment history, medical history, family history, and aspects of quality of life of individuals with Sunflower syndrome. The survey was administered to individuals with Sunflower syndrome who experience hand waving episodes (HWE) and/or their caregivers via Research Electronic Data Capture (REDCap). RESULTS: Sixty-eight responses were included in analysis. Seventy-one% of respondents were female. The mean age of participants was 13.6 years, with 84% of respondents under the age of 18. The average age of onset of HWE was 6.7 years. HWE frequency varied from a few episodes per week to multiple episodes per hour. Sixty-two% of participants experienced other seizure types. Participants had been on an average of 1.9 anti-seizure medications with varying efficacy. Other methods to reduce HWE included wearing a hat or sunglasses, hand holding, using special tinted lenses, and avoiding the sun and bright lights. Sixty-nine% of participants reported anxiety or depression related to their epilepsy, and 65% said their HWE affected their social life. SIGNIFICANCE: Sunflower syndrome is a highly stereotyped, refractory epilepsy which significantly impacts the lives of affected individuals. It remains underrecognized and poorly understood. These results characterize Sunflower syndrome in a large population of affected individuals and provides a basis for future research to better understand the epilepsy and improve clinical care.

Barbiturate derivatives for managing multifaceted oncogenic pathways: A mini review.

Development and progression of metastasis comprises synchronized erroneous expressions of several composite pathways, which are difficult to manage simultaneously with the representative anticancer molecules. The emergence of the drug resistance and the complex interplay between these pathways further potentiates cancer related complexities. Barbiturates and their derivatives present a commendable anticancer profile by attenuating the cancer manifesting metabolic and enzymatic pathways including, but not limited to matrix metalloproteinases, xanthine oxidase, amino peptidases, histone deacetylases, and Ras/mitogen-activated protein kinase. The derivatization and conjugation of barbiturates with pharmacophores delivers a suitable hybrid profile in containing the anomalous expression of these pathways. The present report presents a succinct collation of the barbiturates and their derivatives in managing the various cancer causing pathways.

Changing Fields-Diabetes Medications Invading the Cardiovascular Space.

Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes, and treatment strategies that impact cardiovascular (CV) outcomes in this population is an area of growing interest. Pharmacologic agents that reduce CVD risk have been developed, and data supporting their use have grown extensively. Glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors when added to metformin therapy provide the most CV benefit and should be considered in most patients. Data available suggest that sulfonylureas should be avoided in patients at risk for CVD and if a thiazolidinedione is utilized, pioglitazone may be preferred. When selecting an agent, the potential benefit, risk, and cost of each agent should be considered prior to initiation. The purpose of this review is to summarize the literature surrounding the CV effects of antidiabetic agents and to provide practical guidance on their use in patients with type 2 diabetes and CVD.

Turning Up to Eleven: Factor XI Inhibitors as Novel Agents to Maximize Safety and Maintain Efficacy in Thromboembolic Disease.

Within the past decade nonvitamin K oral anticoagulants have emerged as the standard of care for the prevention and treatment of thromboembolic disorders, however safety of anticoagulants remain a concern for many patients and providers. There exists new interest in factor XI inhibition as novel therapeutic target based on observations of lower thrombotic rates and without significant bleed risk in individuals with inherited factor XI deficiency. Several classes of factor XI inhibitors including antisense oligonucleotides, monoclonal antibodies, and small molecule inhibitors have undergone preclinical studies and clinical trials in humans. Both osocimab and IONIS-FXI have been evaluated in patients undergoing orthopedic surgery and demonstrated superiority to enoxaparin without increasing major bleeding. Future studies with both these agents are ongoing, as well as the continued development of other inhibitors of factor XI. Early data regarding factor XI inhibition is encouraging as a potent anticoagulant and may offer a safer alternative compared to therapeutic currently available in contemporary practice for thromboembolic disease.

Clinical and Economic Implications of Restrictions on Calcitonin Utilization in a Health System.

Background: Hypercalcemia is a relatively common problem that may require hospital admission based on severity. A treatment option for hypercalcemia is calcitonin given intramuscularly or subcutaneously. Purpose: In 2015, calcitonin was on our health system formulary, but due to a sharp rise in cost, restrictions were placed to ensure appropriate utilization. Intervention: These restrictions reserved calcitonin for patients with symptomatic hypercalcemia or severe hypercalcemia, which was defined as an ionized calcium of greater than 1.5 mmol/L and/or total/corrected calcium (Ca) of greater than 13 mg/dL. In addition to providing criteria for its use, calcitonin orders also had an automatic stop date of 24 hours to ensure no more than 2 doses were provided in a 24-hour period. After the initial 24 hours, a patient would have to be reviewed again before any further doses were ordered and administered. If the patient met criteria, an additional 2 doses could be given in the next 24 hours for a total maximum treatment of 4 doses over a 48-hour time frame. Results: An evaluation to assess health system-wide compliance of the usage of calcitonin restrictions regarding utilization, effectiveness, and cost was conducted. In the 2-month study time frame that was examined, there was a decrease in 66 vials of calcitonin that were dispensed. This represents a 43% reduction in usage and an estimated US $450,000 reduction in the total money spent for calcitonin annually. No notable differences in Ca reduction were identified between the groups. Conclusion: This evaluation revealed that putting health system-wide restrictions in use for a high-cost medication can have a major financial impact without compromising clinical efficacy.

Indications and Evidence for Dual Antiplatelet Therapy After Acute Ischemic Stroke.

The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage.

From WOEST to AUGUSTUS: a review of safety and efficacy of triple versus dual antithrombotic regimens in patients with atrial fibrillation requiring percutaneous coronary intervention for acute coronary syndrome.

For patients with atrial fibrillation with concomitant acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI), the increased risk of bleeding associated with the use triple therapy is well established. However, there is question whether it is a necessary risk for patients to prevent stroke and stent thrombosis. The purpose of this article is to highlight the findings of prior studies evaluating the comparative safety and efficacy of dual and triple antithrombotic regimens in the subgroup of atrial fibrillation patients requiring PCI for ACS. Trials that evaluated dual versus triple antithrombotic therapy demonstrated post-PCI treatment with a P2Y12 inhibitor alone was safer than aspirin plus a P2Y12 inhibitor in patients also taking an anticoagulant for atrial fibrillation. Data regarding ischemic outcomes have not suggested harm with the omission of aspirin, but these studies have not been powered to assess efficacy outcomes, especially in ACS patients. These studies also demonstrate a significant reduction in bleeding events when aspirin is excluded from the post-PCI regimen in the ACS subgroup of atrial fibrillation patients. Further studies, with added focus on the ACS subgroup, are needed to potentially confirm that dual therapy may be as efficacious as triple therapy in ACS patients with atrial fibrillation.

Comparison of three antimicrobial strategies in diabetic foot infections post-amputation.

BACKGROUND: The 2012 Infectious Disease Society of America (IDSA) guidelines recommend antimicrobial treatment of diabetic foot infections (DFIs) post-amputation, but the optimal route and duration are poorly defined. OBJECTIVE: The objective of this study was to determine whether the selection of a specific antimicrobial treatment modality affected hospital and patient outcomes. METHODS: This was a retrospective review of hospital admissions of adults admitted to ourhealthcare system with a primary diagnosis of DFIs post-amputation. The groups were separated into patients who received intravenous antimicrobials (IV), oral antimicrobials (PO), or no antimicrobials (NA). Outcomes included average length of stay among others. RESULTS: Of the 200 patients screened, 120 patients were included (IV n = 72; PO n = 20; NA n = 28). No statistically significant differences were identified in average LOS (IV = 9.97 ± 5.85, PO = 8.83 ± 7.37, NA = 9.33 ± 5.91 days; p = 0.73). However, post-operative (post-op) LOS was significantly shorter in the PO group (PO = 3.43 ± 2.56, IV = 7.34 ± 5.95, NA = 5.81 ± 4.18 days; p = 0.0001). CONCLUSION: The results of our study indicate that a PO antimicrobial treatment strategy post amputation for DFIs has the potential to decrease post-op LOS without increasing the risk of readmission. Based on the results of our study, we feel consideration should be given to transition to oral antimicrobials soon after amputation to facilitate discharge and decrease the utilization of intravenous antimicrobials.

Management of Chronic Hypertension Following Intracerebral Hemorrhage.

Acute blood pressure control after a cerebrovascular event is integral in the immediate care of these patients to preserve perfusion to ischemic areas and prevent intracerebral bleeding. The majority of patients with ischemic stroke or intracerebral hemorrhage (ICH) present with preexisting hypertension and therefore require a treatment plan after the acute phase. The presence of chronic hypertension after ICH has often been discussed as a modifiable risk factor for recurrent events. Clinical evidence is relatively lacking for clinicians to understand the extent of blood pressure lowering and the optimal agents to use in this setting. Limited data exist describing the long-term management of hypertension in patients after cerebrovascular events. This review provides nurses with a summary of the available literature on long-term blood pressure management to minimize the risk of secondary ICH and ischemic stroke. It focuses on oral antihypertensive medications available in the United States that may be utilized to manage chronic hypertension immediately after the postacute phase of care to lower blood pressure and to improve long-term outcomes.

Comparison of Parenteral Opioid Dosing in Adult Sickle Cell Disease Patients With Vaso-occlusive Crisis.

Sickle cell disease (SCD) is a chronic condition characterized by multiple vaso-occlusive complications, including acute pain crisis. The mainstay of treatment for patients presenting with vaso-occlusive crisis (VOC) is pain control and adequate hydration. Currently, there are no studies to determine an optimal pain control regimen in adult SCD patients. The main objective of this study is to evaluate whether outcomes differ in patients with VOC based on pain management treatment modality. A retrospective review of admissions with a primary diagnosis of VOC admitted to our facility was conducted. The primary outcome was to compare the average length of stay (LOS) in patients treated with intermittent injection (INT) or patient-controlled analgesia (PCA). Secondary outcomes assessed included 30-day readmission, treatment failure, and impact on pain scores. Of 302 admissions screened, 150 met inclusion criteria (INT: n = 100; PCA: n = 50). Selection of initial pain control regimen showed no difference in average LOS (INT: 5.96 ± 4.19 days vs. PCA: 6.01 ± 3.47 days; P = .94) or 30-day readmission rates (INT: 21% vs. PCA: 16%; P = .52). Treatment failure was significantly higher in the INT group, occurring in 64% of patients vs. 14% in the PCA group (P < .0001). Pain scores were not significantly impacted by selection of pain regimen. Our study indicates that INT and PCA treatment modalities are both effective at controlling pain in VOC; however, more patients in the INT group were characterized as having a treatment failure. Based on our results, it is reasonable to initiate PCA as the primary pain treatment strategy in SCD patients presenting in VOC.

Should Pharmacies Be Included in Medication Reconciliation? A Report of Recurrent Valproic Acid Toxicity.

Including outpatient pharmacies in the medication reconciliation process upon hospital discharge is not commonly performed. This case highlights the consequences of a patient refilling a discontinued prescription for valproic acid (VPA). We present a 32-year old male found unresponsive after ingesting delayed release divalproex sodium. Cerebral edema was visualized on magnetic resonance imaging. Hemodialysis and levo-carnitine treatment led to improved mental status, and VPA was discontinued. The same patient presented with VPA overdose eight months later after he continued to fill an outdated prescription. This case highlights consequences of VPA toxicity; it also demonstrates an opportunity to improve patient safety and high-value care by collaborating with outpatient pharmacies in the medication reconciliation process upon hospital discharge.