bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Therapeutic Drug Monitoring and Pharmacovigilance to Overcome Some of the Challenges of Developing Medicinal Cannabis from Botanical Origins
Authors: Dryburgh Laura M. , Martin Jennifer H.
Published: September 2019

Purpose:

Plants belonging to the genus Cannabis have been domesticated and used by humans for millennia. Thought to have originated from central Asia, cannabis has been harnessed for its nutritional, therapeutic, and psychoactive properties, and as a source of fiber (Office of Medicinal Cannabis. Analytical Monograph Cannabis Flos. Den Haag, The Netherlands: Office of Medicinal Cannabis; 2014). Human use of cannabis is not novel; however, its medicalization offers a new pharmacotherapeutic frontier.

Methods:

The authors recently reported a systematic review of the contaminants of cannabis (National Academies of Sciences Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC; 2017). This article draws on the research limitations identified by that review and examines a collection of the relevant literature to provide an appreciation of the current evidence base.

Results:

The review explores the current status of cannabis in medical use, the drug development aspects that apply when taking a plant through to pill development, and the roles that therapeutic drug monitoring and pharmacovigilance have to guide practice until the drug development information on medicinal cannabis preparations is complete.

Conclusions:

A surge of public and clinical interest in the possible therapeutic applications of constituent cannabinoids has potentiated global legislative and policy reform. However, our understanding of its properties, optimized use, and harmful effects remains incomplete (Therapeutic Goods Administration. Guidance for the use of medicinal cannabis in Australia In: Department of Health Department, editor. Woden ACT Australian Government 2017; Dryburgh LM, Bolan NS, Grof CP, Galettis P, Schneider J, Lucas CJ, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Brit J Clin Pharm. 2018;84(11):2468–2476). In particular, a comprehensive appreciation of its toxicity profile is lacking.
Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study
Authors: Gazzuola Rocca Liliana , Smith Carin Y. , Bobo William V. , Grossardt Brandon R. , Stewart Elizabeth A. , Laughlin-Tommaso Shannon K. , Rocca Walter A.
Published: September 2019

Objective:

We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications.

Methods:

We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression.

Results:

Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001).

Conclusions:

We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies.

Video Summary:

http://links.lww.com/MENO/A458.
Education level and breast cancer incidence: a meta-analysis of cohort studies
Authors: Dong Jia-Yi , Qin Li-Qiang
Published: September 2019

Objective:

We aimed to examine the association between education level and breast cancer incidence by a meta-analysis of cohort studies.

Methods:

Relevant studies were identified by searching PubMed, Web of Science, and Scopus databases on June 10, 2018. Reference lists from the obtained articles were also reviewed. We included cohort studies reporting relative risks with 95% CIs for the association between education level and breast cancer incidence. Either a fixed- or random-effects model was used to calculate the pooled risk estimates.

Results:

We identified 18 cohort studies with more than 10 million women. Compared with women with a lower education level, women with a higher education level had a significantly higher risk of developing breast cancer (pooled relative risk 1.22 [95% CI, 1.14-1.30]). The results did not differ by study area or reference group. The association remained in studies that adjusted for age at first birth and parity, but was attenuated and no longer significant when the analysis was restricted to studies that adjusted for alcohol use, to studies that adjusted for age at menopause, or to studies that adjusted for hormone therapy.

Conclusions:

A higher education level may be associated with an increased risk of developing breast cancer, in which alcohol use, age at menopause, and hormone therapy may, at least partially, play a mediating role.
A Systematic Review and Meta-analysis on PTSD Following TBI Among Military/Veteran and Civilian Populations
Authors: Loignon Alexandra , Ouellet Marie-Christine , Belleville Geneviève
Published: September 2019

Objectives:

To determine whether persons with traumatic brain injury (TBI) are at greater risk of developing posttraumatic stress disorder (PTSD) than other trauma-exposed populations without TBI, and whether this risk is even greater in military/veteran settings than in civilian settings.

Design:

A systematic review and meta-analysis was conducted in 7 databases. Reference lists from the 33 identified studies and other relevant reviews were also searched.

Results:

The pooled PTSD proportion reached 27% (95% confidence interval = 21.8-33.1) in groups with TBI, which was 2.68 times greater than the observed 11% (95% confidence interval = 8.0-15.0) in groups without TBI. PTSD after TBI was more frequently observed in military samples than in civilians (37% vs 16%). Military and civilian samples were respectively 4.18 and 1.26 times more inclined to have a diagnosis of PTSD after TBI than when there was no TBI. The proportion of PTSD after TBI was concurrently attributable to the methods of the included studies (objectives focused on PTSD diagnosis, type of comparison group) and to characteristics specific to the military setting (country, sex, blast injuries).

Conclusions:

TBI diagnosis and military setting represent greater risks for PTSD. The dual diagnosis of TBI and PTSD requires interdisciplinary collaboration, as physical and psychological traumas are closely intertwined.
Pragmatic Language Comprehension After Pediatric Traumatic Brain Injury: A Scoping Review
Authors: Deighton Stephanie , Ju Narae , Graham Susan A. , Yeates Keith Owen
Published: September 2019

Objective:

This scoping review aims to examine the literature pertaining to pragmatic language comprehension in pediatric traumatic brain injury (TBI), in order to summarize the current evidence and to identify areas for further research.

Methods:

We searched MEDLINE Ovid and PsycINFO Ovid using search terms to identify all articles that examined pragmatic language comprehension in children and adolescents with TBI published until November 2017.

Results:

A total of 13 articles met our inclusion criteria. The studies included examined a number of pragmatic domains including knowledge-based and pragmatic inferences, detection and judgment of ambiguous sentences, comprehension of humor, understanding of figurative language (eg, metaphors and idioms), and comprehension of irony and deceptive praise.

Conclusion:

The research suggests that children and adolescents with TBI, as compared with healthy or orthopedically injured controls, display deficits in comprehension of pragmatic language. Children with severe TBI demonstrate more widespread deficits in pragmatic comprehension abilities, whereas children with mild TBI show relatively intact pragmatic comprehension. Limitations and gaps identified in the literature warrant further research in this area.
Evaluation of a Brief, Skill-Building, Supportive, and Educational Intervention for Couples After Brain Injury
Authors: Kreutzer Jeffrey S. , Marwitz Jennifer H. , Sima Adam P. , Graham Kristin M. , Hsu Nancy H. , Mills Ana , Lukow Herman R.
Published: September 2019

Objective:

To examine the effectiveness of an intervention (Therapeutic Couples Intervention, TCI) designed to improve relationship quality for couples after acquired brain injury.

Setting:

Outpatient brain injury rehabilitation center.

Participants:

Persons with brain injury (n = 75) and their intimate partners (n = 75).

Design:

Two-arm parallel, randomized, controlled trial with wait-listed control.

Methods:

Composed of 5 to 6 2-hour sessions, the TCI is a manualized, treatment program designed to enhance relationship quality by addressing issues and concerns most often identified by persons with brain injury and their partners.

Main Measure:

Revised Dyadic Adjustment Scale completed by the persons with brain injury and their partners.

Results:

Persons with brain injury and their partners in the treatment group showed an improvement in relationship quality, both compared with their own baseline values and the control group.

Conclusions:

Investigation provided evidence that a curriculum-based education, skill-building, and supportive intervention can benefit couples for up to 3 months after treatment. Additional research is needed to ascertain the long-term benefits of intervention and the efficacy of alternative delivery methods (eg, Internet, telephone, and group).
Multidisciplinary Concussion Management: A Model for Outpatient Concussion Management in the Acute and Post-Acute Settings
Authors: Bailey Christopher , Meyer Jessica , Briskin Susannah , Tangen Christopher , Hoffer S. Alan , Dundr Jason , Brennan Bethany , Smith Paul
Published: September 2019

Objective:

To describe a model of multidisciplinary concussion management and explore management methods in the acute and post-acute settings.

Setting:

A multidisciplinary concussion management program within a large health system.

Participants:

Patients with sports and non–sports-related concussions aged 14 to 18 years with persisting concussion symptoms at 4 weeks postinjury or beyond.

Design:

Pilot randomized controlled trial comparing a subsymptom threshold exercise program with standard-of-care treatment in the post-acute setting.

Main Measures:

Beck Depression Inventory-II and the Post-Concussion Scale-Revised.

Results:

Across groups, 60% improvement in concussion symptoms was noted. After removing the influence of depression, the intervention showed a large effect on symptom reduction, with participants in the intervention group improving more than those in the control group. There was no difference in response to the intervention by the sports and nonsports groups.

Conclusion:

Results demonstrate that exercise intervention is effective in reducing symptoms in adolescents with persisting symptoms. The finding that participants in the control group who underwent education, light activity, and sophisticated monitoring still had meaningful recovery supports the utility of active engagement in a multidisciplinary management program. Finally, depression had a clinically meaningful effect on recovery, highlighting the need for targeted intervention of noninjury factors relevant to persisting symptoms.
N-Acetyl-Aspartate in the Dorsolateral Prefrontal Cortex Long After Concussion in Youth
Authors: MacMaster Frank P. , McLellan Quinn , Harris Ashley D. , Virani Shane , Barlow Karen M. , Langevin Lisa Marie , Yeates Keith Owen , Brooks Brian L.
Published: September 2019

Objective:

Despite increasing interest in the neurobiological effects of concussion in youth, a paucity of information is available regarding outcomes long after injury. The objective of this study was to determine the association between a history of concussion and the putative neuronal marker N-acetyl-aspartate (NAA) in the dorsolateral prefrontal cortex (DLPFC) in youth.

Setting:

Outpatient clinic in a children's hospital.

Participants:

Youth with concussion (N = 35, mean = 2.63, SD = 1.07 years postinjury) and youth with a nonconcussive orthopedic injury (N = 17) participated.

Design:

A cross-sectional proton magnetic resonance spectroscopy (1H-MRS) study.

Main Measures:

The primary outcome measure was NAA concentration in the right and left DLPFCs.

Results:

We observed lower levels of NAA in the right DLPFC in youth with past concussion (F = 3.31, df = 4,51, P = .018) than in orthopedic controls but not in the left DLPFC (F = 2.04, df = 4,51, P = .105). The effect of lower NAA concentrations in the right DLPFC was primarily driven by youth with a single prior concussion versus those with multiple concussions. NAA in the left DLPFC, but not in right DLPFC, was associated with worse emotional symptoms in youth with concussion.

Conclusion:

The presence of lower levels of DLPFC NAA suggests potential association of concussion in youth, although further investigation is needed, given that the result is driven by those with a single (and not multiple) concussion. Exploration of applying MRS in other brain regions is also warranted.
PHENOTYPIC CHARACTERISTICS OF ROD–CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT
Authors: Khateb Samer , Mohand-Saïd Saddek , Nassisi Marco , Bonnet Crystel , Roux Anne-Françoise , Andrieu Camille , Antonio Aline , Condroyer Christel , Zeitz Christina , Devisme Céline , Loundon Natalie , Marlin Sandrine , Petit Christine , Bodaghi Bahram , Sahel José-Alain , Audo Isabelle
Published: September 2019

Purpose:

To document the rod–cone dystrophy phenotype of patients with Usher syndrome type 1 (USH1) harboring MYO7A mutations.

Methods:

Retrospective cohort study of 53 patients (42 families) with biallelic MYO7A mutations who underwent comprehensive examination, including functional visual tests and multimodal retinal imaging. Genetic analysis was performed either using a multiplex amplicon panel or through direct sequencing. Data were analyzed with IBM SPSS Statistics software v. 21.0.

Results:

Fifty different genetic variations including 4 novel were identified. Most patients showed a typical rod–cone dystrophy phenotype, with best-corrected visual acuity and central visual field deteriorating linearly with age. At age 29, binocular visual field demonstrated an average preservation of 50 central degrees, constricting by 50% within 5 years. Structural changes based on spectral domain optical coherence tomography, short wavelength autofluorescence, and near-infrared autofluorescence measurements did not however correlate with age. Our study revealed a higher percentage of epiretinal membranes and cystoid macular edema in patients with MYO7A mutations compared with rod–cone dystrophy patients with other mutations. Subgroup analyses did not reveal substantial genotype–phenotype correlations.

Conclusion:

To the best of our knowledge, this is the largest French cohort of patients with MYO7A mutations reported to date. Functional visual characteristics of this subset of patients followed a linear decline as in other typical rod–cone dystrophy, but structural changes were variable indicating the need for a case-by-case evaluation for prognostic prediction and choice of potential therapies.
CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY
Authors: Sacconi Riccardo , Bandello Francesco , Querques Giuseppe
Published: September 2019

Purpose:

To report the first case describing choroidal neovascularization in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Methods:

Case report including multimodal imaging discussion.

Results:

A 21-year-old woman affected by LCHAD deficiency (confirmed by 1528 G>C homozygous mutation) was referred to our department for progressive visual decline in both eyes. Best-corrected visual acuities were 20/40 and 20/1,000 in the right and left eye, respectively. Ultra-widefield imaging, fluorescein angiography, structural optical coherence tomography, and optical coherence tomography angiography revealed the presence of macular and midperipheral chorioretinal atrophy complicated by a choroidal neovascularization in the left eye.

Conclusion:

Ocular changes in LCHAD deficiency are long-term complications and severely affect the quality of life of patients. We report for the first time the evidence that choroidal neovascularization could complicate ocular changes accelerating the progressive vision impairment.
Machine-learning–based knowledge discovery in rheumatoid arthritis–related registry data to identify predictors of persistent pain
Authors: Lötsch Jörn , Alfredsson Lars , Lampa Jon
Published: September 2019

Early detection of patients with chronic diseases at risk of developing persistent pain is clinically desirable for timely initiation of multimodal therapies. Quality follow-up registries may provide the necessary clinical data; however, their design is not focused on a specific research aim, which poses challenges on the data analysis strategy. Here, machine-learning was used to identify early parameters that provide information about a future development of persistent pain in rheumatoid arthritis (RA). Data of 288 patients were queried from a registry based on the Swedish Epidemiological Investigation of RA. Unsupervised data analyses identified the following 3 distinct patient subgroups: low-, median-, and high-persistent pain intensity. Next, supervised machine-learning, implemented as random forests followed by computed ABC analysis–based item categorization, was used to select predictive parameters among 21 different demographic, patient-rated, and objective clinical factors. The selected parameters were used to train machine-learned algorithms to assign patients pain-related subgroups (1000 random resamplings, 2/3 training, and 1/3 test data). Algorithms trained with 3-month data of the patient global assessment and health assessment questionnaire provided pain group assignment at a balanced accuracy of 70%. When restricting the predictors to objective clinical parameters of disease severity, swollen joint count and tender joint count acquired at 3 months provided a balanced accuracy of RA of 59%. Results indicate that machine-learning is suited to extract knowledge from data queried from pain- and disease-related registries. Early functional parameters of RA are informative for the development and degree of persistent pain.
Characterization of Student Drinking Behaviors at the Beginning of the First Academic Year at One University in Southern Italy
Authors: De Salvia Maria Antonietta , D'Uggento Angela Maria , Aquilino Giovanni , Tattoli Maria , Finelli Carmine , Imbrici Paola , Desaphy Jean Francois , Giustino Arcangela
Published: September 2019

It is well recognized that both college and noncollege students are at-risk age groups for alcohol consumption. We investigated the alcohol consumption habits of undergraduate students with an emphasis on binge drinking. Participants (N = 809, 61.2% female) were freshmen attending courses at one of the main universities of southern Italy. They were asked to fill out a paper-and-pencil questionnaire that was administered between October 2017 and January 2018. Nearly 90% of the questioned students reported drinking alcohol during the 12 months before the survey. Among them, 31.4% of female students and 41.5% of male students engaged in binge drinking, mainly once a month; binge drinkers preferred highly alcoholic beverages during parties, underestimated the alcoholic content of their drinks, started drinking alcohol at a younger age than nonbinge drinkers, and drank weekly and between meals. Binge drinkers started smoking earlier than their peers, and a great number of them consumed illicit drugs. Moreover, 30.3% of female and 34.8% of male nonbinge drinkers declared that they consumed 6 or more units of alcohol in one occasion, making them unaware binge drinkers. Furthermore, approximately 50% of students recognized that alcohol consumption has effects similar to those induced by illicit drugs but only considered their peers' drinking behavior to be risky.

This study highlights that most students involved in this survey expose themselves to a risky lifestyle by heavy drinking and, most alarmingly, that some of them are not even aware of that.
State of the Art in European Addictions Nursing
Authors: Clancy Carmel , Kelly Peter , Loth Christien
Published: September 2019

In this article, we discuss the state of the art of addiction nursing in Europe. This state is viewed throughout the United Kingdom, Ireland, and the Netherlands and has a direct link to the future. Despite differences, the three countries share nursing values. The start of International Nurses Society in Addictions Nursing Ireland and the Netherlands is only the beginning of a new connection and cooperation Europe-wide.
Individuals With Opioid Dependence Using Polysubstances
Authors: Jaiteh Christine , Steinauer Regine , Frei Irena Anna
Published: September 2019

Background:

Opioid dependence accompanied by polysubstance use is a chronic illness with severe somatic, psychological and social consequences for those affected. International studies have shown that healthcare provision is inadequate for this population because of stigmatization and lack of expertise among medical professionals. It must be assumed that this is also the case in acute care settings of hospitals in German-speaking areas of Switzerland. To date, there are few studies addressing these patients’ experiences that could provide data for targeted interventions.

Aims:

This qualitative study explored this patient population’s perspective in terms of their experiences and needs regarding care provision in acute hospitals. The results should offer potential adaptations to care provision for this vulnerable group of individuals.

Methods:

Twelve individuals with opioid dependence using polysubstances were interviewed in two urban substitution centers. The data analysis of the material obtained was undertaken using qualitative content analysis according to Mayring.

Results:

As a whole, individuals with opioid dependence using polysubstances are not dissatisfied with care provided in acute hospitals as long as their relationship with health professionals is positive. Substitution medication is critically important to their treatment, but this group’s experiences with its management during hospitalization continue to show widespread stigmatization along with inadequate knowledge and interprofessional collaboration and a failure to integrate these patients and their expertise into treatment and care.

Conclusions and Future Directions:

The treatment of individuals with substance-related disorders in acute hospitals requires staff with somatic and psychiatric training. In this regard, the principles of evidence-based models of reducing harm and multiprofessional treatment teams should be seen as particularly well suited and promising.
Disruptive Engagements With Technologies, Robotics, and Caring
Authors: Tanioka Tetsuya , Yasuhara Yuko , Dino Michael Joseph S. , Kai Yoshihiro , Locsin Rozzano C. , Schoenhofer Savina O.
Published: September 2019

Human caring, founded on a Japanese caring perspective and nursing theory, fosters innovative and creative ideas for an aging society. The growing reality of health care dependency on technology presents a temptation to give robots utility as partners in nursing practice. Human caring expressed in human-to-human relationships, and also between humans and nonhumans, is a futuristic model for health care, with humanoid robots as major supporters. The purpose of this article is to explore this disruptive technology, along with its functions and characteristics. Tanioka's Transactive Relationship Theory of Nursing is shared along with its relevance for addressing technological disruptions in health care.
Simulation as a Nursing Education Disrupter
Authors: Waxman KT , Bowler Fara , Forneris Susan Gross , Kardong-Edgren Suzie , Rizzolo Mary Anne
Published: September 2019

Simulation as an evidence-based pedagogy began emerging at a time when many constraints were being imposed on clinical experiences for nursing students. As research illuminated the advantages of simulation and standards were developed, educators began to recognize the limitations of the clinical setting, such as the inability to provide experiences in teamwork and delegation, and a focus on tasks. Simulations are crafted to provide an experience that matches content that is being taught in class, and debriefing techniques guide learners in a reflective process that promotes the development of clinical reasoning and judgment. The National Council of State Boards of Nursing study concluded that simulation could be substituted for 50% of clinical hours. Simulation-exposed gaps in the curriculum and its pedagogical principles are now extending to adaptations of its use in the classroom and in clinical postconferences. They are also shaping teacher-student conversations in the office and the hallways. Use of simulation for assessment is beginning to evolve. In a little more than 10 years, it has started a revolution that will continue to have a major impact on all aspects of nursing education in the future.
Compassion Fatigue and Compassion Satisfaction Among Multisite Multisystem Nurses
Authors: Kawar Lina Najib , Radovich Patricia , Valdez Regina M. , Zuniga Stephen , Rondinelli June
Published: September 2019

Compassion fatigue is a phenomenon that might affect nurses of all specialties. Compassion fatigue occurrence could be profound and costly. The immediate impact could be disruption of the unit culture. This study investigated the prevalence and individual-level factors associated with compassion fatigue among nurses. An upsurge in patients' complexity today may leave nurses stressed with increasing practice demands and vulnerable to compassion fatigue. If ignored, compassion fatigue may compromise nurses' health and care outcomes. A sample of 1174 nurses from 2 large Southern California health care organizations completed an online survey measuring compassion fatigue, burnout, and compassion satisfaction. Overall, participants scored moderate to average (23–41) on compassion satisfaction, burnout, and compassion satisfaction. Experienced and working nights nurses experienced higher compassion satisfaction levels. Higher compassion fatigue means were associated with new graduates = 29.5, BSN nurses = 27.2, ICU nurses = 27.4, and working 12-hour shift nurses = 26.9, suggesting higher compassion fatigue vulnerability. Nurse leaders and managers can apply this baseline evidence to create tailored programs for specific nursing specialties and inexperienced nurses to tackle compassion fatigue and reduce related unit disorder. Seasoned nurses' perspective can be of value in enhancing those efforts.
Evolution of Care and Nursing
Authors: Preziosi Peter , Shaffer Franklin A.
Published: September 2019

Health care costs are growing exponentially. They will continue to erode disposable income, especially among those most in need of health care—the poor and elderly. As the baby boomer generation ages, we will see dramatic growth in health care spending, which will influence the health care market in new ways. Increased government intervention and technological advancements will only further this shift. Factors driving the need for health care transformation include fragmentation, access problems, unsustainable costs, suboptimal outcomes, and disparities of care. Nurses now have more tools (ie, mHealth, telemedicine, and electronic health records) that they can use to provide assistance to their practices outside of acute care settings. These realities are all contributors to an evolving trend: retail health.
Virtual Nursing: The New Reality in Quality Care
Authors: Schuelke Sue , Aurit Sarah , Connot Nancy , Denney Shannon
Published: September 2019

The purpose of this article is to report on an innovative new model of care and the effects this model pilot program had on patient satisfaction, staff satisfaction, physician satisfaction, patient quality metrics, and financial metrics. The Virtually Integrated Care team is a model of care that leverages technology to bring an experienced expert nurse into the patients' room virtually. The advanced technology allows the virtual nurse to direct and monitor patient care, interacting with the patient through 6 core roles: patient education, staff mentoring/education, real-time quality/patient safety surveillance, physician rounding, admission activities, and discharge activities.
Disrupt Now for Future Focus
Authors: Sullivan Lauren , Yoder-Wise Patricia S.
Published: September 2019

Health care organizations are challenged by numerous and rapid changes. Although nurse leaders seldom lead the whole organization's response to these changes, most changes impact the nursing workforce. To be prepared and proactive, nurse leaders need to consider the process of disrupting what the nursing workforce does to keep current with what society expects of nursing.
Glial Fibrillary Acidic Protein (GFAP) Autoimmunity in the Setting of Seropositive Rheumatoid Arthritis Treated With Etanercept
Authors: Smith Kelsey M. , Amin Shreyasee , Jones Lyell K. , Lachance Daniel H. , Flanagan Eoin P. , Jentoft Mark E. , Kantarci Orhun H.
Published: September 2019

Introduction:

Glial fibrillary acidic protein (GFAP) immunoglobulin G is a recently discovered biomarker of an autoimmune central nervous system disorder characterized by a steroid-responsive meningoencephalomyelitis.

Case Report:

A 63-year-old man with rheumatoid arthritis on etanercept presented with steroid-responsive subacute encephalopathy and foot drop. Brain and sural nerve biopsies demonstrated a T-cell perivascular infiltrate. Cerebrospinal fluid studies 18 months into the course of the illness demonstrated a GFAP antibody on mouse tissue immunofluorescence confirmed by cell-based assay. The patient was treated with steroids and cyclophosphamide leading to resolution of his symptoms.

Conclusion:

This case expands on the previously reported cases of GFAP immunoglobulin G autoimmunity by describing an associated inflammatory large fiber peripheral neuropathy.
Afatinib, an irreversible ErbB family blocker for the treatment of epidermal growth factor receptor mutation-positive non-small cell lung cancer
Authors: Summers Yvonne , Graham Donna M.
Published: September 2019

Targeted inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as the standard of care for EGFR mutation-positive non-small cell lung cancer (EGFRm+ NSCLC). Afatinib, an oral irreversible ErbB-family blocker, has been extensively studied in this context. Recent studies have highlighted the benefit and tolerability of afatinib treatment in patients with EGFRm+ advanced/metastatic NSCLC. The LUX-Lung 3 and 6 phase III studies showed greater efficacy with first-line afatinib compared with platinum-doublet chemotherapy, whereas LUX-Lung 7 highlighted the enhanced benefits of afatinib over the first-generation EGFR tyrosine kinase inhibitor (TKI), gefitinib. The nearly inevitable emergence of resistance to afatinib, coupled with recent data for the third-generation TKI osimertinib, highlight the need to identify an optimal treatment sequencing strategy to achieve long-term benefit and survival. The available data suggest that optimal treatment could involve first-line afatinib, followed by osimertinib upon acquired resistance to afatinib through the T790M mutation. This review discusses the pharmacology of afatinib, efficacy and safety results of key trials in the afatinib clinical study program, management of adverse events, and sequencing strategies following acquired resistance. Afatinib data are discussed in the context of recent studies of other EGFR TKIs, to provide considerations around their use and inform potential sequential treatment approaches.
Experience with Combining Pediatric Procedures into a Single Anesthetic
Authors: Miketic Renata M. , Uffman Joshua , Tumin Dmitry , Tobias Joseph D. , Raman Vidya T.
Published: September 2019

Introduction:

The combination of multiple procedures within a single anesthetic may provide many challenges for the perioperative team. Coordination of specialties, consideration for parental time burdens, and travel expenses as well as limiting multiple anesthetic exposures to the children are pertinent factors to consider when advocating the combination of surgical procedures.

Methods:

The electronic medical record at Nationwide Children’s Hospital was retrospectively queried to obtain information on patients having a single anesthetic encounter for 2 or more procedures involving 2 or more services over 1 year (July 2015–June 2016).

Results:

One thousand one hundred twenty patients had 2 procedures during a single anesthetic encounter. The average anesthesia time was 127 ± 102 minutes, and average PACU time was 64 ± 37 minutes. The unanticipated admission rate was 85 of 1,120 cases (7.6%). Five (6%) of the unanticipated admission cases were ASA status 1, 33 (39%) were ASA status 2, and 47 (55%) were ASA status ≥3; compared with 87 (9%), 481 (50%), and 391 (41%) in the group not requiring unanticipated admission (P = 0.032) (see Fig. 1).

Conclusions:

These data demonstrate the feasibility of combining several procedures during a single anesthetic encounter and may result in decreased healthcare costs as well as limitation of parental cost and time obligations.
Red Cell Distribution Width and Mean Platelet Volume in Patients With Ankylosing Spondylitis
Authors: Deng Jixiang , Xu Shanshan , Gao Xing , Xu Shengqian , Shuai Zongwen , Pan Faming
Published: September 2019

Objective

The results of previous studies regarding the relationship between red cell distribution width (RDW) or mean platelet volume (MPV) levels and ankylosing spondylitis (AS) are inconsistent. Therefore, we conducted this meta-analysis to systematically evaluate the associations.

Methods

The Web of Science, PubMed, and Cochrane Library (as of February 14, 2019) were used to retrieve relevant articles. Pooled standard mean difference (SMD) and its 95% confidence interval (CI) were calculated. All statistical analyses were performed using the “meta” and “metafor” packages of the R 3.5.1 software.

Results

Nine studies on RDW, including 775 AS patients and 972 healthy controls, and 8 studies on MPV, including 743 AS patients and 571 healthy controls, were included. The results showed that RDW levels were significantly higher in AS patients (SMD = 0.67; 95% CI, 0.30 to 1.05; p < 0.001) compared with healthy controls, whereas MPV levels (SMD = 0.01; 95% CI, −0.28 to 0.30; p = 0.929) were not significantly different from healthy controls.

Conclusions

Our current study shows that the elevated levels of RDW may be associated with AS, whereas MPV levels may be not associated with AS
Preoperative Ultrasonographic Staging of Papillary Thyroid Carcinoma With the Eighth American Joint Committee on Cancer Tumor-Node-Metastasis Staging System
Authors: Zhang Jingwen , Fei Mengjia , Dong Yijie , Xu Shangyan , Zhan Weiwei
Published: September 2019

Objective

The purpose of this study was to evaluate the performance of preoperative ultrasonography (US) in the staging of papillary thyroid carcinoma (PTC) according to the eighth AJCC TNM classification system, to determine the effect of the preoperative US staging in the management of PTC.

Patients and Methods

Preoperative US was performed by 2 highly trained sonographers in 665 consecutive patients with PTC, and the T and N categories were determined preoperatively. The accuracy of preoperative US in clinical staging was evaluated based on the histopathological specimens according to the eighth AJCC TNM classification. Further analysis was performed to identify the high-risk factors of N1b stage.

Results

Overall accuracy of preoperative US for T stage was 92.5% (615/665). The accuracy of sonographic evaluation for T was high except for the T4a. Overall accuracy of preoperative US for N stage was 59% (426/655). The accuracies of sonographic evaluation for N0, N1a, and N1b were 81.8% (274/335), 33.3% (70/250), and 87.5% (70/80), respectively. Of 250 N1a patients, 164 (65.6%) were underestimated by US. Univariate and multivariate analyses showed that larger tumor diameter, multifocality, and higher T stage significantly increase the risk of N1b stage (P < 0.01).

Conclusions

Preoperative US was useful for the evaluation in staging of PTC, but some limitations still existed. For higher-risk patients of N1b (larger tumor size, multifocality, and higher T stage), preoperative US examination for lateral neck region should be further emphasized, and prophylactic lateral nodal dissection should be determined based on both preoperative imaging results and intraoperative evaluation.
Transfusion of Anaerobically or Conventionally Stored Blood After Hemorrhagic Shock
Authors: Williams Alexander T. , Jani Vivek P. , Nemkov Travis , Lucas Alfredo , Yoshida Tatsuro , Dunham Andrew , D’Alessandro Angelo , Cabrales Pedro
Published: September 2019

Background:

Resuscitation from hemorrhagic shock (HS) by blood transfusion restores oxygen (O2) delivery and provides hemodynamic stability. Current regulations allow red blood cells (RBCs) to be stored and used for up to 42 days. During storage, RBCs undergo many structural and functional changes. These storage lesions have been associated with adverse events and increased mortality after transfusion, increasing the need for improved RBC storage protocols. This study evaluates the efficacy of anaerobically stored RBCs to resuscitate rats from severe HS compared with conventionally stored RBCs.

Methods and results:

Rat RBCs were stored under anaerobic, anaerobic/hypercapnic, or conventional conditions for a period of 3 weeks. Hemorrhage was induced by controlled bleeding, shock was maintained for 30 min, and RBCs were transfused to restore and maintain blood pressure near the prhemorrhage level. All storage conditions met current regulatory 24-h posttransfusion recovery requirements. Transfusion of anaerobically stored RBCs required significantly less RBC volume to restore and maintain hemodynamics. Anaerobic or anaerobic/hypercapnic RBCs restored hemodynamics better than conventionally stored RBCs. Resuscitation with conventionally stored RBCs impaired indices of left ventricular cardiac function, increased hypoxic tissue staining and inflammatory markers, and affected organ function compared with anaerobically stored RBCs.

Conclusions:

Resuscitation from HS via transfusion of anaerobically stored RBCs recovered cardiac function, restored hemodynamic stability, and improved outcomes.
Multivalent proteins rapidly and reversibly phase-separate upon osmotic cell volume change
Authors: Jalihal Ameya P. , Pitchiaya Sethuramasundaram , Xiao Lanbo , Bawa Pushpinder , Jiang Xia , Bedi Karan , Parolia Abhijit , Cieslik Marcin , Ljungman Mats , Chinnaiyan Arul M. , Walter Nils G.
Published: September 2019

Processing bodies (PBs) and stress granules (SGs) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration that adapts the cell to volume change.

GRAPHICAL ABSTRACT

IN BRIEF

Cells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.

HIGHLIGHTS

DCP1A undergoes rapid and reversible hyperosmotic phase separation (HOPS)

HOPS of DCP1A depends on its trimerization domain

Self-interacting multivalent proteins (valency ≥ 2) undergo HOPS

HOPS of CPSF6 explains transcription termination defects during osmotic stress
NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells
Authors: Madsen Ralitsa R. , Longden James , Knox Rachel G. , Robin Xavier , Völlmy Franziska , Macleod Kenneth G. , Moniz Larissa S. , Carragher Neil O. , Linding Rune , Vanhaesebroeck Bart , Semple Robert K.
Published: September 2019

Activating PIK3CA mutations are known “drivers” of human cancer and developmental overgrowth syndromes. We recently demonstrated that the “hotspot” PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In the present study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of PIK3CAH1047R homozygous cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling dose, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant transcriptomic signature of TGFβ pathway activation in PIK3CAH1047R heterozygous was observed but was modest and was not associated with the stemness phenotype seen in homozygous mutants. Notably, the stemness gene expression in PIK3CAH1047R homozygous iPSCs was reversed by pharmacological inhibition of TGFβ signalling, but not by pharmacological PI3Kα pathway inhibition. Altogether, this provides the first in-depth analysis of PI3K signalling in human pluripotent stem cells and directly links dose-dependent PI3K activation to developmental NODAL/TGFβ signalling.
Determining organ weight toxicity with Bayesian causal models: Improving on the analysis of relative organ weights
Authors: Lazic Stanley E. , Semenova Elizaveta , Williams Dominic P.
Published: September 2019

Regulatory authorities require animal toxicity tests for new chemical entities. Organ weight changes are accepted as a sensitive indicator of chemically induced organ damage, but can be difficult to interpret because changes in organ weight might reflect chemically-induced changes in overall body weight. A common solution is to calculate the relative organ weight (organ to body weight ratio), but this inadequately controls for the dependence on body weight – a point made by statisticians for decades, but which has not been widely adopted. The recommended solution is an analysis of covariance (ANCOVA), but it is rarely used, possibly because both the method of statistical correction and the interpretation of the output may be unclear to those with minimal statistical training. Using relative organ weights can easily lead to incorrect conclusions, resulting in poor decisions, wasted resources, and an ethically questionable use of animals. We propose to cast the problem into a causal modelling framework as it directly assesses questions of scientific interest, the results are easy to interpret, and the analysis is simple to perform with freely available software. Furthermore, by taking a Bayesian approach we can model unequal variances, control for multiple testing, and directly provide evidence of safety.
IGF1R undergoes active and directed centripetal transport on filopodia upon receptor activation
Authors: Krndija Denis , Fairhead Michael
Published: September 2019

Filopodia are thin, actin-based membrane protrusions with roles in sensing external mechanical and chemical cues, such as growth factor gradients in tissues. It was proposed that the chemical sensing role of filopodia is achieved through clearance of activated signaling receptors from filopodia. Type I insulin-like growth factor receptor (IGF1R) is a key regulator of normal development and growth, as well as tumor development and progression. Its biological roles depend on its activation upon IGF1 binding at the cell membrane. IGF1R behavior at the cell membrane and in particular in filopodia, has not been established. We found that IGF1 activation led to a gradual reduction in IGF1R puncta in filopodia, and that this clearance depended on actin, non-muscle myosin II, and IGF1R kinase activity. Using single particle tracking of filopodial IGF1R, we established that ligand-free IGF1R undergoes non-directional unidimensional diffusion along the filopodium. Moreover, after initial diffusion, the ligand-bound IGF1R is actively transported along the filopodium towards the filopodium base, and consequently cleared from the filopodium. Our results show that IGF1R can move directionally on the plasma membrane protrusions, supporting a sensory role for filopodia in interpreting local IGF1 gradients.
Automatic press-fit assembly of small precision interference fitting parts: armature of electro-hydraulic servo valve
Authors: Wang Xingyuan , Lou Zhifeng , Wang Xiaodong , Wang Yue , Hao Xiupeng , Wang Zhize
Published: September 2019

Purpose

The purpose of this paper is to design an automatic press-fit instrument to realize precision assembly and connection quality assessment of a small interference fitting parts, armature.

Design/methodology/approach

In this paper, an automatic press-fit instrument was developed for the technical problems of reliable clamping and positioning of the armature, automatic measurement and adjustment of the attitude and evaluation of the connection quality. To compensate for the installation error of the equipment, corresponding calibration method was proposed for each module of the instrument. Assembly strategies of axial displacement and perpendicularity were also proposed to ensure the assembly accuracy. A theoretical model was built to calculate the resistant force generated by the non-contact regions and then combined with the thick-walled cylinder theory to predict the press-fit curve.

Findings

The calibration method and assembly strategy proposed in this paper enable the press-fit instrument to achieve good alignment and assembly accuracy. A reasonable range of press-fit curve obtained from theoretical model can achieve the connection quality assessment.

Practical implications

This instrument has been used in an armature assembly project. The practical results show that this instrument can assemble the armature components with complex structures automatically, accurately, in high-efficiency and in high quality.

Originality/value

This paper provides a technical method to improve the assembly quality of small precision interference fitting parts and provides certain methodological guidelines for precision peg-in-hole assembly.