An Emergency Department Quality Improvement Project for Intravenous Levetiracetam Administration.

Background: Levetiracetam is a readily available, safe anticonvulsive medication. It is frequently administered as IV piggyback with a pump, carrier fluid, and tubing. The Established Status Epilepticus Treatment Trial demonstrated levetiracetam being similarly effective to previously used treatments in doses up to 4500 mg administered over 10 minutes. Objective: We sought to compare usage, cost, and waste of IV piggyback with IV push administration of levetiractam following implementation of an IV push protocol in an academic emergency department. Methods: A three-month review of levetiracetam administration was done following protocol implementation using IV push for initial treatment of benzodiazepine-refractory status epilepticus. The review quantified the number of IV push vs IV piggyback doses for all indications and evaluated cost of supplies necessary for administration. Results: During the study period, 137 patients received 142 doses of IV levetiracetam. Fifty-one doses (36%) were given as IV push rather than IV piggyback. The majority of doses 116 (82%) were 1000-2000 mg and 11 doses (8%) 3500-4500 mg. Estimated three-month savings with complete transition of IV piggyback to IV push would exceed $6000 just in our ED. The amount of sterile solution carrier fluid was also reduced and IV pump time freed. Conclusion: Implementation of an emergency department IV push levetiracetam protocol resulted in cost savings. Opportunities remain to improve clinical implementation practices. Medication administration represents one crucial target area where healthcare systems can implement policies to reduce waste and commit to climate-smart health care.

Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.

BACKGROUND: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. METHODS: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. RESULTS: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. CONCLUSIONS: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation.

Healing experience for family caregivers after an intensive care unit death.

OBJECTIVES: Family caregivers suffer a high burden of emotional and psychological distress following the death of a loved one in the intensive care unit and often struggle to heal in the weeks following their loss. The purpose of this hermeneutic phenomenological study was to describe and interpret the experience of healing for family caregivers six weeks following the death of a loved one in the ICU. METHODS: Semi-structured telephone interviews were conducted with a purposive sample of twenty-four family caregivers six weeks following the death of their loved ones in the ICU. Qualitative analysis techniques were used to identify common themes central to the experience of healing across all interviews. RESULTS: Seven themes were interpreted from the data: searching for clarity from a time of uncertainty; riding an emotional rollercoaster; seeking peace in one's decisions; moving forward with each new day; taking comfort in the memories; valuing layers of support; and discovering life on one's own. CONCLUSION: By identifying and gaining an understanding of healing following the death of a loved one in the ICU, nursing and other healthcare providers have an opportunity to promote healing and positively impact family caregiver's bereavement.

Evaluation of First-Dose, Intravenous Push Penicillins and Carbapenems in the Emergency Department.

BACKGROUND: Early appropriate antibiotic administration is associated with improved outcomes in infectious illnesses. During drug shortages in 2017, the American Society of Health-System Pharmacists recommended intravenous push (IVP) administration of medications when possible to conserve small-volume parenteral solutions. Data supporting IVP penicillins and carbapenems was limited. OBJECTIVE: The primary objective of this study compared time from patient emergency department (ED) arrival to antibiotic administration between IVP and intravenous piggy-back (IVPB) administration. METHODS: This single-center pre-post protocol study assessed changes in administration timing and safety of ampicillin/sulbactam, piperacillin/tazobactam, and ertapenem from 2015-2018. Medication administration by IVPB (pre) or IVP (post), ED arrival, antibiotic order and administration times, potential effectors of administration time, and safety events were assessed. Acquisition costs were estimated. RESULTS: A total of 696 administrations were included, with 351 and 345 subjects in the IVPB and IVP cohorts, respectively. The median time from ED arrival to initiation of antibiotic administration was 140 (IQR 87-221) minutes and 110 (IQR 68-181) minutes in the IVPB and IVP cohorts, respectively, (P < 0.01). IVP administration increased the proportion of indexed antibiotics administered within 60 minutes of ED arrival compared to IVPB (20% vs. 12%, respectively, P < 0.01). There was no difference in adverse events between both cohorts. Supply acquisition cost savings totaled an more than $5,000 with the IVP protocol. CONCLUSION: IVP administration of ampicillin/sulbactam, piperacillin/tazobactam, and ertapenem improved times to initiation of empiric, first-dose antibiotics in the ED without an increase in adverse events, saving over $5,000 annually.

Gene characterization and expression of the γδ T cell co-receptor WC1 in sheep.

Sheep are known to express the hybrid co-receptor/pattern recognition receptor WC1 on their γδ T cells but details of the ovine WC1 multigenic array and gene expression were unknown. Annotation of the sheep genome assembly (Oar_rambouillet_v1.0) yielded 15 complete and 42 partial WC1 genes predicted to code for six different protein structures. RT-PCR amplification of the most distal scavenger receptor cysteine rich (SRCR) domain known as a1, which serves as the gene signature, from genomic and cDNA templates verified the majority of annotated genes. As for cattle and goats, sheep a1 domain sequences included WC1.1 and WC1.2 types. A unique ovine gene, WC1-16, had multiple SRCR a-pattern domains in tandem similar to one found in goats. Intracytoplasmic domains of WC1 transcripts had splice variants that may affect signal transduction. The larger number of WC1 genes in sheep and differences in structures and splice variants relative to cattle could have implications in expression patterns and engagement of γδ T cells by pathogens or vaccine constructs.

Efficacy and safety of topical capsaicin for cannabinoid hyperemesis syndrome in the emergency department.

Introduction: Cannabinoid hyperemesis syndrome (CHS) is a disorder of cyclic and recurrent nausea, vomiting, and abdominal pain associated with high-frequency and extended-duration marijuana use. Standard antiemetic therapy is often ineffective; however, capsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1), has shown promise in treating CHS.Methods: This retrospective cohort analysis evaluated the safety and efficacy of topical capsaicin for patients presenting with CHS. The primary outcome was to assess if utilization of capsaicin for ED management of CHS decreased ED length of stay (LOS) as compared to a visit without capsaicin. Secondary outcomes included a cost analysis, use of rescue therapies, and adverse events.Results: Forty-three patients met the inclusion criteria within the study period. ED LOS was reduced with capsaicin by a median of 22 minutes (201 vs. 179 min, p = 0.33). Patients received fewer additional medications if capsaicin was utilized (4 vs. 3 doses, p = 0.015), and 67% of visits where capsaicin was utilized required no further treatment prior to discharge. Additionally, opioid usage was less when utilizing capsaicin (166.5 vs. 69 mg OME). Forty-two percent of patients did not have a repeat CHS presentation to the ED after receiving capsaicin for an additional three months after the study period ended. Total medication cost was minimally more expensive (median difference of $3.26) in the capsaicin group. There were no significant adverse events reported with capsaicin.Conclusion: There was no significant difference in ED LOS when capsaicin was utilized for CHS. However, there was a decrease in total medications administered and a reduction in opioid requirements. While medication costs for capsaicin visits were minimally more expensive, the utility of capsaicin as an over-the-counter (OTC) product may empower at home therapy with OTC products, decreasing potentially unnecessary healthcare encounters and costs.

Intravenous Push Cephalosporin Antibiotics in the Emergency Department: A Practice Improvement Project.

Delays in administration of appropriate antibiotics to patients with septic shock are associated with increased mortality. To improve the care of patients with sepsis within our 73-bed emergency department (ED), a "first-dose" intravenous push (IVP) cephalosporin antibiotic protocol was initiated. This project was aimed at improving the time from provider order of antibiotic to administration, which follows the Sepsis Core Measure of timely antibiotic administration.This was a single-center, retrospective analysis of a practice improvement study. Time from provider order of an IV cephalosporin antibiotic to administration was compared between postprotocol dates of March to May 2016 (n = 1110) and preprotocol dates of November 2015 to January 2016 (n = 1146). The cost of supplies for IVP was compared with traditional infusion. Prior to implementation of the IVP protocol, ED nursing staff completed a survey of administration preferences and then received one-on-one instruction about the protocol from the clinical nurse specialist and clinical nurse educator. In addition, a tip sheet was developed and IVP kits complete with all needed supplies were made available in the automated medication dispensing system.Median time from IV cephalosporin antibiotic order to administration significantly decreased by 8, 12, 14, and 13 min for ceftriaxone, ceftazidime, cefepime, and cefazolin, respectively (p < 0.007 for all). This was true for all indications of antibiotic use. Nursing staff favored IVP administration over traditional IV infusion (87%). Supply cost to administer IVP antibiotics was $0.83 compared with $9.53 for traditional IV infusion.A "first-dose IVP" protocol decreased time to administration by eliminating the need for procurement of an infusion pump, setup, and documentation of a secondary infusion. It was also preferred by ED nursing staff and associated with cost savings.

Improved Administration of Antibiotics in the Emergency Department: A Practice Improvement Project.

PROBLEM: Although consensus exists among experts that early intravenous antibiotic therapy has an impact on patient mortality, the medical literature includes little information about ensuring that the patient receives the complete dose. At our emergency department, it had become standard clinical practice to administer antibiotics with primary pump tubing and an infusion pump. Clinical pharmacy staff identified this practice as a cause for concern, because at least 20 mL (up to 40%) of the dose volume remains in the tubing. This practice improvement project was aimed at improving the administration of antibiotics by programming a secondary infusion to ensure the complete dose would be administered. METHODS: A multidisciplinary educational intervention was initiated consisting of one-on-one instruction with each emergency nurse (n = 103) at the department's annual Skills Sessions, distribution of educational tip sheets, and reinforcement of the proper procedure at the patient's bedside. Emergency nurses were educated via simulation regarding correct secondary pump programming, using smart pump technology. RESULTS: Surveys indicated that 8% of emergency nurses used secondary tubing along with a smart pump to administer antibiotics before the intervention, compared with 96% after the intervention (P < .0001). IMPLICATIONS FOR PRACTICE: This project demonstrates that our educational intervention improved awareness of the need to administer the entire antibiotic dose and adherence to the use of secondary tubing along with smart pump technology to administer antibiotics.

Why is the sex gap in feelings of depression wider in high gender equity countries? The effect of children on the psychological well-being of men and women.

This study uses data from 23 countries in the World Values Survey and the National Survey of Families and Households and finds that the sex gap in feelings of depression is wider in high gender equity societies even though overall levels of feelings of depression are lower. Using hierarchical logistic modeling, we find that the sex difference in feelings of depression is wider in high gender equity societies because children increase depression for women in high gender equity societies, while they reduce depression for women without paid employment in low gender equity societies. There is little difference in the effect of children on feelings of depression for men across societies.

Religion and the quality of life in the last year of life.

OBJECTIVES: Religious involvement in old age appears to remain quite stable until the very end of life, reflecting patterns established earlier in life. Are there differences in quality of life (QOL) for those who are religiously involved in that last year compared with those who are not? METHODS: We studied 499 elderly persons participating in ongoing annual interviews who died in the 12 months following an interview. We examined public and subjective religious involvement and indicators of health-related and psychosocial QOL, including health status and functional ability, family and friendship networks, depression, and well-being. RESULTS: More deeply religious respondents were more likely to see friends, and they had better self-rated health, fewer depressive feelings, and were observed by the interviewer to find life more exciting compared with the less religious. Respondents receiving strength and comfort from religion reported poorer self-rated health. Those who attended religious services often were most likely to have attended holiday parties, even after adjusting for health status. Significant interactions indicated that the disabled benefited more from both public and subjective religious involvement than the nondisabled. DISCUSSION: Overall, QOL in the last year of life is positively related to religious involvement, particularly its more subjective dimensions.

Preoperative and intraoperative risk factors associated with 30-day morbidity following urological surgery: the National Surgical Quality Improvement Program.

PURPOSE: The National Surgical Quality Improvement Program was established in 1994 to measure and enhance of the quality of surgical care. Since its inception, 30-day postoperative morbidity after major surgery in the Veterans Administration has decreased by 45%. We performed a pilot study to assess risk factors associated with 30-day morbidity using National Surgical Quality Improvement Program indicators in a private setting. MATERIALS AND METHODS: A total of 643 subjects were accrued by a trained surgical reviewer from our institution between December 2003 and December 2004. Patient preoperative, intraoperative and nonNational Surgical Quality Improvement Program data elements were abstracted from clinical records. Bivariate relationships between preoperative risk factors, intraoperative process measures and 30-day postoperative morbidity were determined. Multiple variable logistic regression analysis was used to identify patient preoperative and intraoperative risk factors associated with 30-day morbidity. RESULTS: On multivariate analysis the preoperative risk factors history of congestive heart failure (OR 14.42, 95% CI 2.66 to 78.30), diabetes with end organ damage (OR 12.56, 95% CI 2.09 to 75.53), angioplasty (OR 2.75, 95% CI 1.27 to 5.93), quadriplegia (OR 4.39, 95% CI 1.36 to 14.14), low albumin (OR 2.49, 95% CI 1.18 to 5.24) and hydronephrosis (OR 2.51, 95% CI 1.11 to 5.69) were statistically significant predictors of 30-day postoperative morbidity. Intraoperative process measures, that is operative time in hours (OR 1.24, 95% CI 1.12 to 1.37) and transfusion (OR 3.11, 95% CI 1.49 to 6.50), were also significant contributors to postoperative morbidity. CONCLUSIONS: We found that patient preoperative risk factors and intraoperative process measures were important determinants of postoperative morbidity. Implementation of the National Surgical Quality Improvement Program in urology may be used to measure processes of care that are associated with surgical outcomes and, thereby, improve the quality of urological care.

Sexual behavior, sexually transmitted diseases and prostatitis: the risk of prostate cancer in black men.

PURPOSE: Black men are diagnosed with prostate cancer more often than white men, present with more advanced disease and have worse stage specific survival. Given the high risk of incidence and mortality in this population, determining potentially modifiable factors is important. Recent studies have suggested a link between chronic inflammation and development of prostate cancer. In concurrence, population based studies of white men have revealed an increased risk of prostate cancer with history of sexually transmitted diseases and prostatitis. MATERIALS AND METHODS: We explored the chronic inflammation hypothesis of prostate cancer development among black men by examining sexual activity, sexually transmitted diseases and prostatitis in a population based study of 129 patients and 703 controls 40 to 79 years old. RESULTS: After adjusting for age, income, cigarette smoking, and history of digital rectal examination and prostate specific antigen tests in the last 5 years, we observed that a history of gonorrhea infection and prostatitis increased the odds of prostate cancer 1.78-fold (95% CI 1.13, 2.79) and 4.93-fold (95% CI 2.79, 8.74), respectively. Men reporting 25 or more sexual partners were 2.80 (95% CI 1.29, 6.09) times more likely to be diagnosed with cancer compared to men with 5 or fewer partners. CONCLUSIONS: Our findings support the significance of prior sexual practices, exposure to sexually transmitted microbial agents and history of prostatic infection in the natural history of prostate cancer in black men. Additional prospective research incorporating serological markers of infectious agents or predictive markers of chronic inflammation should serve to elucidate the possible causal pathway of recurring or persistent infection in the etiology of prostate cancer in black men.

Low insulin-like growth factor-II levels predict weight gain in normal weight subjects with type 2 diabetes.

PURPOSE: Insulin-like growth factor (IGF)-I and IGF-II are important in the regulation of metabolism and growth. We previously reported in normoglycemic individuals of normal weight that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of type 2 diabetes. METHODS: In 224 subjects with type 2 diabetes we assessed the association between baseline IGF-II levels and risk of weight gain (>2.0 kg) at the 5-year follow-up. RESULTS: At follow-up, 90 participants (40.2%) gained more than 2.0 kg in body weight. For subjects (body mass index <26) at baseline, mean IGF-II levels were significantly lower in those who gained more than 2 kg in weight than in subjects of stable weight, 454 ng/mL (95% confidence interval 349-559) versus 620 ng/mL (534-705) (F=7.4, P=.01). For this subgroup low circulating IGF-II at baseline strongly correlated with weight gain (Spearman rho=-0.52, P <.001). With increasing weight, the relationship no longer prevailed. Logistic regression showed that for body mass index less than 26, individuals at baseline for each 100 ng/mL increase in baseline IGF-II there was a 47% decreased risk of gaining 2.0 kg or more in weight. Adjustment for treatment group did not materially alter this relationship. There was no difference in baseline IGF-II by treatment group. There was no difference between the group with weight gain and the group with stable weight in those who additionally received insulin or sulfonylurea treatment in the 5 years between the baseline visit and the follow-up. CONCLUSIONS: In subjects of normal weight with type 2 diabetes, baseline IGF-II concentration is inversely related to future weight gain, independent of treatment effect, strengthening the putative role for IGF-II in regulating fat mass. We propose that IGF-II measurement has potential utility in this group for targeting such individuals for early intervention.

In sickness but not in health: self-ratings, identity, and mortality.

Self-rated health as a predictor of mortality has been studied primarily in large, representative populations, with relatively little progress toward understanding the information processing that individuals use to arrive at these ratings. With subsamples of National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study (NHEFS) data for respondents with circulatory system disease (N = 3,709) and respondents with no diagnosable disorders (N = 1,127) at baseline, we test the idea that individuals with experience of chronic disease of the circulatory system will have more predictive self-ratings of health than healthy individuals. Poor or fair self-rated health increased the adjusted hazard of all-cause mortality for respondents with circulatory system disease, but not for respondents who were healthy. Additional analyses confirm that poor or fair self-rated health is particularly predictive for respondents with self-reported history of circulatory system diagnoses and perception of symptoms, but not for respondents without symptoms or diagnoses prior to the NHANES physical exam.

Longitudinal changes in lower urinary tract symptoms among a cohort of black American men: the Flint Men's Health Study.

OBJECTIVES: To examine the progression of lower urinary tract symptoms in a longitudinal population-based cohort of black men. Population-based studies of prostatism and longitudinal data regarding changes in lower urinary tract symptom severity have largely focused on white men, with little attention directed toward black men. METHODS: In 1996, a probability sample of 369 black men, aged 40 to 79 years, residing in Genesee County, Michigan, and without a prior history of prostate cancer/surgery participated in a prostate cancer screening protocol that included completing the American Urological Association Symptom Index (AUASI). Four years after baseline, 175 of the 369 men agreed to participate in the follow-up protocol. Of the 175 men, 149 had not reported undergoing treatment for benign prostatic hyperplasia and had complete symptom data. These men were included in this study. Differences between baseline and follow-up AUASI scores were examined. RESULTS: The mean and standard deviation AUASI scores at baseline and follow-up were 7.1 (6.4) and 7.0 (6.8), respectively. Although overall no statistically significant change was found in the mean AUASI during the 4 years of follow-up (-0.11; SD 6.2; P = 0.7), the average change in the symptom score and the variability in the change increased with patient age at baseline from a mean of -0.42 (SD 5.0) among men in their 40s to 2.1 (SD 6.6) among men in their 70s. Of the 91 men (61.1%) who reported mild to no symptoms (AUASI score 7 or less) at baseline, 24 (26.4%) reported moderate to severe symptoms (AUASI score 8 or more) at follow-up. This progression of symptom severity was observed across all ages. CONCLUSIONS: In this population-based study of longitudinal changes in urinary symptoms in black men, we found a substantial percentage of men demonstrated a measurable progression in urinary symptom severity over time. Additional studies are needed to examine critically any racial differences in lower urinary tract symptom progression.