bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategy and risk sharing in hospital–postacute care integration
Authors: McHugh John P. , Zinn Jacqueline , Shield Renee R. , Tyler Denise A. , Gadbois Emily A. , Soni Sneha , Mor Vincent
Published: July 2018

Issue/Trend:

Postacute care has been identified as a primary area for cost containment. The continued shift of payment structures from volume to value has often put hospitals at the forefront of addressing postacute care cost containment. However, hospitals continue to struggle with models to manage patients in postacute care institutions, such as skilled nursing facilities or in home health agencies. Recent research has identified postacute care network development as one mechanism to improve outcomes for patients sent to postacute care providers. Many hospitals, though, have not utilized this strategy for fear of not adhering to Centers for Medicare & Medicaid Services requirements that patients are given choice when discharged to postacute care.

Managerial Approach:

A hospital’s approach to postacute care integration will be dictated by environmental uncertainty and the level of embeddedness hospitals have with potential postacute care partners. Hospitals, though, must also consider how and when to extend shared savings to postacute care partners, which will be based on the complexity of the risk-sharing calculation, the ability to maintain network flexibility, and the potential benefits of preserving competition and innovation among the network members. For hospital leaders, postacute care network development should include a robust and transparent data management process, start with an embedded network that maintains network design flexibility, and include a care management approach that includes patient-level coordination.

Conclusion:

The design of care management models could benefit from elevating the role of postacute care providers in the current array of risk-based payment models, and these providers should consider developing deeper relationships with select postacute care providers to achieve cost containment.
A relational perspective on care coordination
Authors: Ghaffari Affan , Wells Rebecca , Creel Liza , Siañez Mónica
Published: July 2018

Background:

Care coordination occurs largely through care coordinators’ interactions with patients and community partners to identify and address patients’ individual needs. More frequent and higher-quality communication with each may enhance care coordination effectiveness.

Purpose:

The purpose of this study was to understand (a) how care coordinator perceptions of interactions with patients and community partners, respectively, compared to each other group’s perceptions of their interactions with care coordinators and (2) whether these dynamics between care coordinators and community partners changed over time.

Methodology:

The research context was a comparative case study of provider-based care coordination projects funded through the Texas 1115(a) Medicaid waiver. The Relational Coordination instrument was administered through (a) two waves of in-person interviews with care coordinators (2014–2015 and 2015–2016) at a total of 10 sites across the state, (b) a single 2016 phone survey with 159 patients at nine of those sites, and (c) phone surveys with representatives of the community resources that care coordinators had identified as key partners in 2014–2015 and again in 2015–2016.

Results:

Care coordinators reported more frequently needing both patients and community partners than either other group reported relative to care coordinators. Frequency of need and mutual influence with community partners increased in the first 2 years of the care coordination programs’ implementation. The perceived quality of interactions between care coordinators and both patients and community partners was positive, but with room for improvement.

Conclusion:

Care coordination may entail limited interactions with patients and community partners, especially at program inception. As care coordination programs mature, interactions may become more frequent and influence with partners may expand.

Practice Implications:

Decision makers should support care coordinators in improving the quality of their communication with both patients and community partners, as well as allow time for these relationships to develop.
Indoor and Outdoor Radon Concentration Levels in Lebanon
Authors: Habib Rima R. , Nuwayhid Rida Y. , Hamdan Zena , Alameddine Ibrahim , Katul Gabriel
Published: July 2018

Lebanon’s lung cancer rates, among the highest in the Arab region, contribute to the burden of noncommunicable diseases. A number of studies have shown that lung cancer risk increases when smokers vs. nonsmokers exposed to elevated radon levels are compared. This research employs indoor and outdoor space and time concentration surveys across Lebanon, where the smoking rate among the population is among the highest in the world. The distributional properties of measured radon concentration were shown to be lognormal with median indoor and outdoor concentrations of 17 and 10 Bq m−3, respectively. Standard deviation for indoor concentrations was 1.2 times smaller than its outdoor counterpart, suggesting that weather-related patterns affect outdoor radon concentration variability. No significant spatial association was detected across seasons for indoor and outdoor radon concentrations. Geographical location, proximity to faults, and housing construction material had no significant impact on outdoor and indoor radon concentration variations. When lognormal distributions were used to determine exceedance probability of the recommended reference radon concentration, they were smaller than 0.1%. While exhibiting high seasonal variability, the study shows that radon does not appear to be a public health concern in Lebanon.
Unexpected Cardiac MRI Findings in Patients Presenting to the Emergency Department for Possible Acute Coronary Syndrome
Authors: Ziegler Cole E. , Painter David M. , Borawski Joseph B. , Kim Raymond J. , Kim Han W. , Limkakeng Alexander T.
Published: July 2018

Background:

Stress cardiac magnetic resonance imaging (CMR) has become increasingly used in patients presenting to the emergency department (ED) with symptoms concerning for acute coronary syndrome (ACS). We hypothesized that CMR detects a number of alternative diagnoses (diagnoses other than ACS that could explain symptoms) and incidental findings in patients presenting to the ED for potential ACS.

Methods:

We prospectively enrolled adult patients who presented to an academic ED from 2011 to 2015 for possible ACS and subsequently had an adenosine stress perfusion CMR as part of their diagnostic evaluation. All medical charts were reviewed to verify accurate prospective data collection and to collect follow-up data.

Results:

A total of 391 patients were included. On stress CMR, abnormalities attributable to coronary artery disease (CAD) were found in 106 (27.1%) of patients. Previously undiagnosed moderate to severe valvular disease was the most common non-CAD cardiac finding, occurring in 20 (5.1%) cases. Other alternative diagnoses were rare with 7 cases of cardiomyopathy, 1 case of aortic aneurysm, 1 case of aortic dissection, 1 case of acute myocarditis, 3 cases of pericarditis, and 2 cases of moderate pleural effusion. Cardiac incidental findings were rare. Extracardiac incidental findings were found in 79 patients (20.2%). Only 18.6% of the patients recommended for follow-up imaging had this completed within 1 year after CMR.

Conclusions:

This experience suggests that stress CMR is useful in not only diagnosing symptomatic CAD but also potentially important non-CAD–related disease. These factors may impact their use in ED-based ACS workups.
Risk of Motor Vehicle Collision or Driving Impairment After Traumatic Brain Injury: A Collaborative International Systematic Review and Meta-Analysis
Authors: Chee Justin N. , Hawley Carol , Charlton Judith L. , Marshall Shawn , Gillespie Ian , Koppel Sjaan , Vrkljan Brenda , Ayotte Debbie , Rapoport Mark J.
Published: July 2018

Objective:

To synthesize knowledge of the risk of motor vehicle collision (MVC) following a traumatic brain injury (TBI) and the associated risk of driving impairment, as measured by on-road tests, computerized simulators, and self-reported or state-recorded driving records.

Methods:

Our international team searched 7 databases for studies published between 1990 and 2015 of people with TBI, controls, and data concerning either MVC or driving impairment. The included articles examined the risk of MVC among people with TBI; we excluded studies that examined the risk of having a TBI associated with being involved in an MVC.

Results:

From 13 578 search results, we included 8 studies involving 1663 participants with TBI and 4796 controls. We found no significant difference in the risk of MVC (odds ratio = 1.24, 95% confidence interval = 0.80-1.91, P = .34). When we restricted the analysis to self-report, the risk of MVC was higher for those without a TBI (odds ratio = 1.63, 95% confidence interval = 1.21-2.22, P = .002). In contrast, participants with TBI consistently performed worse during on-road assessments and had more problems with vehicular control.

Conclusion:

Limitations of reviewed studies included small sample sizes, failure to specify TBI severity or time postinjury, and absence of objective measures of risk. Findings concerning the relationship between TBIs from non-MVC causes and crash risk are, therefore, inconclusive and do not provide evidence for major changes to existing clinical guidelines for driving with TBI.
Effect of Sex on Recovery From Persistent Postconcussion Symptoms in Children and Adolescents Participating in an Active Rehabilitation Intervention
Authors: Gauvin-Lepage Jérôme , Friedman Debbie , Grilli Lisa , Gagnon Isabelle
Published: July 2018

Objective:

To estimate the extent to which biologic sex contributes to the severity of postconcussion symptoms (PCSs) in concussed youth, who are slow to recover and who receive an active rehabilitation intervention (ARI) as part of their standard care.

Setting:

The concussion clinic of a pediatric trauma center in Canada.

Participants:

A total of 355 youth with persistent PCS (188 girls and 167 boys) as per the following criteria: (1) diagnosed with a concussion (or mild traumatic brain injury) as per the 2004 World Health Organization definition; (2) aged 8 to 17 years (mean = 14.34, standard deviation [SD] = 2.22 years); (3) presenting with at least 1 PCS interfering with daily activities (mean total PCS score at initial assessment = 24.50, SD = 18.88); and (4) on ARI 4 weeks postinjury (mean = 30.46, SD = 3.74 days).

Design:

A retrospective analysis of a prospective cohort.

Main Measures:

PCS severity, measured by the PCS Scale (PCSS) included in the Sports Concussion Assessment Tool-3, was the dependent variable. PCSs were assessed 3 times over a 4-week period.

Results:

Boys presented with significantly fewer symptoms than girls 4 weeks postinjury, at initiation of the ARI (PCSS total score mean: ♂ = 19.9, ♀ = 28.5,P< .001, confidence interval = −14.8 to −6.4), at 2 and 4 weeks of follow-up, but the rate of recovery was slightly faster for girls over the follow-up period.

Conclusion:

Despite differences between the PCSS score reduction after 4 weeks of intervention, our results favored to a slightly faster recovery for girls over the follow-up period. Although our findings are not strong enough to suggest distinct sex-specific intervention, both boys and girls benefit from participating in an ARI.
VASCULARIZED SARCOID GRANULOMA COMPLICATED BY PLACOID DISEASE IN A PEDIATRIC PATIENT
Authors: Pichi Francesco
Published: July 2018

Purpose:

To report a case of pediatric vascularized sarcoid choroidal granuloma complicated by placoid-like inflammation.

Methods:

Case report.

Results:

A 10-year-old girl presented with blurry vision in her right eye and a yellowish macular lesion that had been diagnosed as fibrotic choroidal neovascular membrane and observed for several months. On referral to our clinic, optical coherence tomography revealed a homogeneous hyperreflective lesion obliterating the choroidal vasculature and protruding under the retina with associated subretinal and intraretinal fluid. Optical coherence tomography angiography revealed vascularization of this granulomatous lesion, and the girl underwent six intravitreal injections of anti–vascular endothelial growth factor, with reabsorption of the fluid and consolidation of the lesion. A sudden, abrupt decrease in the visual acuity of the right eye 3 months after the last injection was accompanied on optical coherence tomography by hyperreflective inflammatory lesions breaking from the retinal pigment epithelium and involving the outer nuclear layer, all around the fibrotic granulomatous lesion. The girl was treated with oral steroids, and an extensive systemic evaluation revealed hilar adenopathy, thus posing the diagnosis of pediatric sarcoidosis complicated by placoid chorioretinopathy.

Conclusion:

Atypical presentations of typical uveitic diseases are quite common in children. The presence of a foveal vascularized granuloma complicated by a placoid disorder should prompt the exclusion of infectious etiologies such as tuberculosis, to establish a therapy to preserve the child's vision.
ATL
Authors: Zhu Xinxin , Zhao Ling , Lang Jinghe
Published: July 2018

Objective

This study aimed to assess the relationship between BRCA1 gene methylation, PD-L1 protein expression, and the clinicopathologic features of sporadic ovarian cancer (OC).

Methods

Bisulfite pyrosequencing and immunohistochemistry were used to detect BRCA1 gene methylation and PD-L1 protein expression, respectively, in tumor tissues from 112 patients with sporadic OC. Their levels were analyzed against clinicopathologic characteristics and prognosis using standard statistical methods.

Results

Twenty percent (22/112) of the OC cases exhibited BRCA1 gene hypermethylation. The frequency of BRCA1 hypermethylation was significantly higher in serous OC (25%) than in nonserous OC (8%; P < 0.05). No significant correlations were discovered between BRCA1 hypermethylation and age, menstrual status, tumor location, stage, lymph node metastasis, and prognosis (P > 0.05). Among the 112 OC cases, 59% (66/112) cases were positive for PD-L1 protein expression. No significant difference existed between PD-L1 expression and age, menstrual status, histological type, tumor location, stage, lymph node metastasis, and prognosis (P > 0.05). Moreover, no correlation existed between BRCA1 methylation and PD-L1 expression (P > 0.05, r = 0.002).

Conclusions

This is the first study linking BRCA1 hypermethylation variability to PD-L1 protein expression and the clinicopathologic features of OC. The data demonstrated that an epigenetic alteration of BRCA1 was closely associated with serous OC. The expression of PD-L1 was unrelated to the clinicopathologic features or BRCA1 hypermethylation in sporadic OC.
A Novel Use of Trypan Blue During Canalicular Glaucoma Surgery to Identify Aqueous Outflow to Episcleral and Intrascleral Veins
Authors: Laroche Daniel , Nortey Andrea , Ng Chester
Published: July 2018

Purpose:

We describe a novel technique comprising the use of trypan blue to confirm aqueous outflow to collector channels and aqueous veins after goniotomy with the Kahook Dual Blade (New World Medical, Rancho Cucamonga, CA). Intraocular dyes have been safely used during ophthalmic surgery to evaluate the patency of the trabecular meshwork and collector channels. Further, trypan blue has been safely used to stain the anterior capsule of the lens in cataract surgery, to enhance visualization for capsulorhexis; similarly, trypan blue has been safely used to stain the trabecular meshwork for enhanced visualization during glaucoma angle surgery. Channelography enables evaluation of the collector channels during canaloplasty with fluorescein dye; episcleral fluid wave enables evaluation of the intraoperative structural patency of the conventional outflow system, from the anterior chamber to the episcleral and conjunctival distal collectors after Trabectome goniotomy (NeoMedix Corporation, Tustin, CA).

Patients and Methods:

We evaluated 4 cases of glaucoma patients who underwent goniotomy with the Kahook Dual Blade to observe whether trypan blue could identify the patency of Schlemm’s canal and aqueous egress to episcleral and intrascleral veins.

Results:

We successfully confirmed the outflow pathway via Schlemm’s canal and collector channels with trypan blue in 3 of the 4 cases.

Conclusions:

We conclude that trypan blue can be used safely to confirm both aqueous outflow and the patency of Schlemm’s canal and aqueous veins during canalicular glaucoma surgery.
Molecular therapy for genetic and degenerative vestibular disorders
Authors: Sayyid Zahra N. , Kim Grace S. , Cheng Alan G.
Published: July 2018

Purpose of review

The primary purpose of this review is to summarize current literature in the field of vestibular regeneration with a focus on recent developments in molecular and gene therapies.

Recent findings

Since the discovery of limited vestibular hair cell regeneration in mammals in the 1990s, many elegant studies have improved our knowledge of mechanisms of development and regeneration of the vestibular system. A better understanding of the developmental pathways of the vestibular organs has fueled various biological strategies to enhance regeneration, including novel techniques in deriving vestibular hair cells from embryonic and induced pluripotent stem cells. In addition, the identification of specific genetic mutations responsible for vestibular disorders has opened various opportunities for gene replacement therapy.

Vestibular dysfunction is a significant clinical problem with limited therapeutic options, warranting research on biological strategies to repair/regenerate the vestibular organs to restore function. The use of gene therapy appears promising in animal models of vestibular dysfunction.
Regulatory B cells and transplantation: almost prime time?
Authors: Mohib Kanishka , Cherukuri Aravind , Rothstein David M.
Published: July 2018

Purpose of review

Regulatory B cells (Bregs) are potent inhibitors of the immune system with the capacity to suppress autoimmune and alloimmune responses. Murine transplant models showing that Bregs can promote allograft tolerance are now supported by clinical data showing that patients who develop operational tolerance have higher frequency of Bregs. Breg function has been widely studied resulting in improved understanding of their biology and effector mechanisms. However, our overall understanding of Bregs remains poor due the lack of specific marker, limited knowledge of how and where they act in vivo, and whether different Breg subpopulations exhibit different functions.

Recent findings

In this review we detail murine and human phenotypic markers used to identify Bregs, their induction, maintenance, and mechanisms of immune suppression. We highlight recent advances in the field including their use as biomarkers to predict allograft rejection, in-vitro expansion of Bregs, and the effects of commonly used immunosuppressive drugs on their induction and frequency.

Clinical data continue to emerge in support of Bregs playing an important role in preventing transplant rejection. Hence, it is necessary for the transplant field to better comprehend the mechanisms of Breg induction and approaches to preserve or even enhance their activity to improve long-term transplant outcomes.
Analysis of Prognostic Factors in Pancreatic Metastases
Authors: Ito Takashi , Takada Ryoji , Omoto Shunsuke , Tsuda Motoyuki , Masuda Daisuke , Kato Hironari , Matsumoto Toshihiko , Moriyama Ichiro , Okabe Yoshinobu , Shiomi Hideyuki , Ishida Etsuji , Hatamaru Keiichi , Hashimoto Shinichi , Tanaka Kiyohito , Kawamoto Hirofumi , Yanagisawa Akio , Katayama Toshiro , Yazumi Shujiro
Published: July 2018

Objectives

Pancreatic metastases (PMs) account for 1% to 2% of pancreatic tumors, and their prognostic significance is poorly defined. We evaluated the incidence and clinical characteristics of primary tumors and defined prognostic factors.

Methods

This retrospective study of 39 Japanese tertiary referral hospitals (January 2005 to August 2015) analyzed patient and tumor characteristics and survival time. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival and prognostic factors, respectively.

Results

We enrolled 159 patients with a pathologic diagnosis of PM. The most common primary tumor was renal cell carcinoma (38.4%), followed by lung cancer (24.5%), colorectal cancer (11.3%), and sarcoma (6.3%). Eight patients were lost during follow-up, and 151 patients were included for statistical analysis. Median overall survival was 43.0 months, and the 5-year survival rate was 42.6%. Multivariate analysis identified 3 independent prognostic factors: extrapancreatic metastasis (hazard ratio, 2.13; 95% confidence interval, 1.11–4.07; P = 0.02), tumor-related symptoms at diagnosis (hazard ratio, 5.39; 95% confidence interval, 2.92–9.91; P < 0.001), and pathologic diagnosis of primary tumors (P < 0.001).

Conclusions

Treatment strategies and prognoses for PMs completely differ according to the primary tumor type. A definitive pathologic diagnosis of PMs is essential for selecting the appropriate treatment.
Early Predictors of Abdominal Hemorrhage Among Critically Ill Patients With Pancreatitis
Authors: Labarca Eduardo , Zubia Felix , Maraví-Poma Enrique , Martinez Felipe
Published: July 2018

Objective

To establish incidence, risk factors, and prognostic implications of abdominal hemorrhage (AH) among critically ill patients with acute pancreatitis (AP).

Methods

Prospective cohort study in 46 intensive care units aimed at describing the characteristics of critically ill patients with AP (Epidemiología de la Pancreatitis Aguda en Medicina Intensiva Study). Adult patients with AP and at least 1 organ failure were included. The presence of AH was established either by using computed tomography, magnetic resonance imaging, or by direct visualization during surgery. Statistical analyses were carried out using multivariate logistic regression.

Results

Three hundred seventy-four patients were studied. Most were men (62.6%), with a mean (standard deviation) age of 60.4 (15.6) years. Most episodes (56.4%) of AP were severe, and 28.9% died during their hospital stay. Thirty-eight patients (10.2%; 95% confidence interval, 7.3%-13.7%) developed AH. The odds of presenting AH was influenced by age, the underlying cause of pancreatitis, and the presence of shock or respiratory failure on admission.

Conclusions

Abdominal hemorrhages were common among critically ill patients with pancreatitis. These early predictors may be of use in detecting patients at risk of developing them.
Long-term Remission of Acute Myeloid Leukemia Developed From Systemic Mastocytosis by Conventional Chemotherapy
Authors: Yamada Ai , Kinoshita Mariko , Sawa Daisuke , Saito Yusuke , Kamimura Sachiyo , Miyachi Hayato , Moritake Hiroshi
Published: July 2018

Systemic mastocytosis (SM) is a disorder characterized by abnormal proliferation of mast cells withKITmutations, especially in codon 816. The prognosis of patients developing acute myeloid leukemia (AML) from SM is extremely poor, and hematopoietic cell transplantation is recommended. Herein, we describe a case of an 8-year-old female diagnosed with SM developing AML. AKITM541L variant in SM was identified in leukemic cells, normal hematopoietic cells, and buccal mucosal cells, suggesting a germline polymorphism. The patient has remained in complete remission for 39 months after completion of chemotherapy. SM developing AML without aKITD816 mutation may be not necessarily associated with a poor prognosis.
Long-term Outcome After Doxorubicin and Ifosfamide Overdose in a Patient With Osteosarcoma and BARD1 Mutation
Authors: Savani Malvi , Skubitz Keith M.
Published: July 2018

Current treatment of high-grade osteosarcoma consists of preoperative chemotherapy, typically using some combination of doxorubicin, cisplatin, ifosfamide, and/or high-dose methotrexate followed by surgical resection. In this report, we present a case of a 21-year-old woman with high-grade osteosarcoma of the chest wall who received 5 times the planned dose of doxorubin and 4 times the planned dose of ifosfamide. She survived this chemotherapy overdose after administration of dimethyl sulfoxide and phenobarbital. Despite the administration of 5 times the proposed dose of doxorubicin, the patient survived without cardiotoxicity, and later delivered a normal baby. Although there are many studies evaluating treatment for chemotherapy regimen-related toxicity, sparse data exist with respect to chemotherapy overdose and the appropriate course of action. This case further confirms the lower cardiotoxicity of continuous intravenous infusion of doxorubicin and provides support for the use of dimethyl sulfoxide in the prevention of toxicity in chemotherapy overdose.
A Cognitive-Behavioral Intervention for the Symptom Clusters of Chinese Patients With Gastrointestinal Tract Cancer Undergoing Chemotherapy
Authors: Zhang Xinqiong , Wang Qin , Zhang Xiaomin , Wu Xiaoting , Wang Qiuping , Hong Jingfang
Published: July 2018

Background

Patients with gastrointestinal tract (GIT) cancer undergoing chemotherapy often experience several symptoms that constitute symptom clusters and can cause patients to suffer. Effective interventions are lacking for this kind of patients.

Objective

The aims of this study were to test the feasibility and acceptability of a cognitive-behavioral (CB) intervention developed for Chinese patients with GIT cancer undergoing chemotherapy and to estimate the efficacy of the intervention for symptom clusters.

Methods

In this pilot, quasi-randomized controlled trial, 40 patients were assigned to the CB intervention or control group. The CB intervention, considering characteristics of patients and Chinese culture, contained 4 sections including cognitive reframing, cancer-diet education, relaxation, and exercise techniques. Symptom clusters, illness perception, anxiety, and depression were measured.

Results

Thirty-nine patients (97.5%) completed the study program and expressed willingness to follow the intervention. Compared with the control group, all outcomes were improved (all P < .05) in the CB group after the intervention, except for the gastrointestinal symptom cluster (t = 0.25, P = .802). In the CB group, the scores of all outcomes (all P < .05) decreased except for depression (t = 1.76, P = .095).

Conclusion

The CB intervention is partially feasible and acceptable. It may also help to improve part of the symptom clusters of Chinese patients with GIT cancer undergoing chemotherapy. However, some modifications are needed in future studies to better test effectiveness.

Implications for Practice

Symptom management remains a major problem in clinical nursing. Such a CB intervention can be beneficial to the clinical management of symptom clusters.
Efficacy of Pelvic Floor Muscle Training in Women With Overactive Bladder Syndrome: A Systematic Review
Authors: Monteiro Silvia , Riccetto Cassio , Araújo Angélica , Galo Laryssa , Brito Nathália , Botelho Simone
Published: July 2018

(Abstracted from Int Urogynecol J 2018; doi: 10.1007/s00192-018-3602-x)

In the adult population, the prevalence of symptoms in an overactive bladder (OAB) is approximately 17%. In women, it can reach 50%.
Toddler With Intermittent Abnormal Behavior
Authors: Sharawat Indar Kumar , Dawman Lesa
Published: July 2018

Psychosis is a state of altered behavior and mentation, and it is rarely reported in preschool children. Isoniazid is a commonly used drug in the treatment and prophylaxis of tuberculosis. It may cause psychosis in overdose but rarely with usual recommended doses. We report a case of drug-induced psychosis secondary to isoniazid intake in a 3-year-old child. She developed intermittent abnormal behavior for 2 weeks after intake of isoniazid. Drug-induced psychosis was a possibility, and the responsible drug was stopped. She improved following the withdrawal of isoniazid.
Analgesic Efficacy of Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe Pain in Children
Authors: Quinn Kellie , Kriss Sabina , Drapkin Jefferson , Likourezos Antonios , Pushkar Illya , Brady Jason , Yasavolian Matthew , Chitnis Salil S. , Motov Sergey , Fromm Christian
Published: July 2018

Purpose

This study aimed to compare analgesic efficacy of intranasal (IN) ketamine to IN fentanyl for moderate to severe pain in children in a pediatric emergency department.

Methods

A prospective, randomized, double-blinded, noninferiority study evaluating children aged 3 to 17 years in a pediatric emergency department with acute moderate to severe pain was conducted. Patients received either 1 mg/kg of IN ketamine or 1.5 μg/kg of IN fentanyl and were evaluated after 10, 20, 30, and 60 minutes. The primary outcome was the degree of pain reduction after 20 minutes.

Results

Twenty-two patients were enrolled (11 in each group). Underlying pain conditions represented were musculoskeletal injury (73%) and abdominal pain (27%). At 20 minutes after analgesia, there was no significant difference in pain scores between the fentanyl (median, 2; range, 0–8) and ketamine groups (median, 4; range, 0–7;P= 0.20). The ketamine group showed a significantly greater rate of adverse effects, 73% versus 9% (P= 0.002), and throughout the course of the study period, 7 patients in the ketamine group (64%) group showed some degree of sedation versus no one in the fentanyl group (P= 0.004).

Conclusions

There was insufficient power to support the analgesic noninferiority of IN ketamine at a dose of 1 mg/kg compared with IN fentanyl at a dose of 1.5 μg/kg in children experiencing painful conditions at 20 minutes after administration. Intranasal ketamine was found to be inferior to IN fentanyl in relieving pain at 10 minutes and was found to have significantly greater rates of sedation and dizziness.
Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial
Authors: Jespersen Sanne , Hønge Bo Langhoff , Krarup Henrik , Medstrand Patrik , Sørensen Allan , Medina Candida , Té David da Silva , Correira Faustino Gomes , Erikstrup Christian , Østergaard Lars , Wejse Christian , Laursen Alex Lund ,   for the Bissau HIV Cohort study group
Published: July 2018

Background:

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1–infected patients in Guinea-Bissau.

Methods:

This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1–infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment.

Results:

Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52].

Conclusions:

In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.
Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
Authors: Córdoba-Moreno Marlina O. , Todero María Florencia , Fontanals Adriana , Pineda Gonzalo , Daniela Montagna , Yokobori Noemí , Ramos María Victoria , Barrientos Gabriela , Toblli Jorge E. , Isturiz Martín A. , Rearte Bárbara
Published: July 2018

Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxicshock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.
Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1)
Authors: Hidaka Masaaki , Eguchi Susumu , Okuda Koji , Beppu Toru , Shirabe Ken , Kondo Kazuhiro , Takami Yuko , Ohta Masayuki , Shiraishi Masayuki , Ueno Shinichi , Nanashima Atsushi , Noritomi Tomoaki , Kitahara Kenji , Fujioka Hikaru
Published: July 2018

Objective:

The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010.

Background:

Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported.

Methods:

A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified.

Results:

A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis.

Conclusions:

Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.
Management of chronic inflammatory demyelinating polyradiculopathy
Authors: Doneddu Pietro E. , Nobile-Orazio Eduardo
Published: July 2018

Purpose of review

To review the recent advances in the management and treatment of chronic inflammatory demyelinating polyradiculopathy (CIDP).

Recent findings

Recent studies confirm the efficacy/safety of long-term intravenous immunoglobulin (IVIg) and short-term subcutaneous immunoglobulin (SCIg) therapy in CIDP. New outcome measures have been recently proposed and further studies evaluated the properties of those already in use. The presence of antibodies against proteins at the node of Ranvier was associated with specific clinical features and treatment response. Fingolimod adds to the list of immunosuppressive agents that failed to be effective in a controlled trial.

Several studies evaluating the best strategy to provide maintenance IVIg treatment in CIDP are in progress. SCIg were shown to be an alternative to IVIg for maintenance treatment while their efficacy as initial therapy should be further addressed. New outcome measures have been shown to be effective in detecting treatment response in clinical trials, but their use in clinical practice remains uncertain. Similarly unsettled is the role of nerve imaging techniques as biomarker in CIDP. The discovery of antibodies against proteins at the node of Ranvier has rekindled a keen interest in the pathogenesis of CIDP and the potential therapeutic role of new agents.
Winning the arms race: host–parasite shared evolutionary history reduces infection risks in fish final hosts
Authors: Sheath Danny J. , Dick Jaimie T. A. , Dickey James W. E. , Guo Zhiqiang , Andreou Demetra , Britton J. Robert
Published: July 2018

Parasite manipulation of intermediate hosts evolves to increase parasite trophic transmission to final hosts, yet counter selection should act on the final host to reduce infection risk and costs. However, determining who wins this arms race and to what extent is challenging. Here, for the first time, comparative functional response analysis quantified final host consumption patterns with respect to intermediate host parasite status. Experiments used two evolutionarily experienced fish hosts and two naive hosts, and their amphipod intermediate hosts of the acanthocephalan parasite
Pomphorhynchus tereticollis
. The two experienced fish consumed significantly fewer infected than non-infected prey, with lower attack rates and higher handling times towards the former. Conversely, the two naive fish consumed similar numbers of infected and non-infected prey at most densities, with similar attack rates and handling times towards both. Thus, evolutionarily experienced final hosts can reduce their infection risks and costs via reduced intermediate host consumption, with this not apparent in naive hosts.
Joan Mary Anderson. 12 May 1932—28 August 2015
Authors: Horton Peter , Chow Wah Soon , Barrett Christopher
Published: July 2018

Joan Mary (Jan) Anderson pioneered the investigation of the molecular organization of the plant thylakoid membrane, making seminal discoveries that laid the foundations for the current understanding of photosynthesis. She grew up in Queenstown, New Zealand, obtaining a BSc and MSc at the University of Otago in Dunedin. After completing her PhD at the University of California, she embarked on a glittering career at CSIRO and then the Australian National University in Canberra. Not only a gifted experimentalist, Jan was a creative thinker, not afraid to put her insightful and prophetic hypotheses into the public domain. Her many notable achievements include establishing the details and the physiological significance of lateral heterogeneity in the distribution of the two photosystems between stacked and unstacked thylakoid membranes and the dynamic changes in the extent of stacking that occur in response to changes in the light environment. Her investigations brought her into collaboration with leading researchers throughout the world. Recognized with many honours as a leading scientist in Australia, international recognition included the Lifetime Achievement Award from the International Society of Photosynthesis Research and honorary fellowships at universities in the UK and USA.
Dynamic modulation of external conditions can transform chemistry into logic gates
Authors: Egbert Matthew , Gagnon Jean-Sébastien , Pérez-Mercader Juan
Published: July 2018

We introduce a new method for transforming chemical systems into desired logical operators (e.g. NAND gates) or similar signal-manipulation components. The method is based upon open-loop dynamic regulation, where external conditions such as feed-rate, lighting conditions, etc., are modulated according to a prescribed temporal sequence that is independent of the input to the network. The method is first introduced using a simple didactic model. We then show its application in transforming a well-stirred cubic autocatalytic reaction (often referred to as the Selkov–Gray–Scott model) into a logical NAND gate. We also comment on the applicability of the method to biological and other systems.
Evaluation of mechanistic and statistical methods in forecasting influenza-like illness
Authors: Kandula Sasikiran , Yamana Teresa , Pei Sen , Yang Wan , Morita Haruka , Shaman Jeffrey
Published: July 2018

A variety of mechanistic and statistical methods to forecast seasonal influenza have been proposed and are in use; however, the effects of various data issues and design choices (statistical versus mechanistic methods, for example) on the accuracy of these approaches have not been thoroughly assessed. Here, we compare the accuracy of three forecasting approaches—a mechanistic method, a weighted average of two statistical methods and a super-ensemble of eight statistical and mechanistic models—in predicting seven outbreak characteristics of seasonal influenza during the 2016–2017 season at the national and 10 regional levels in the USA. For each of these approaches, we report the effects of real time under- and over-reporting in surveillance systems, use of non-surveillance proxies of influenza activity and manual override of model predictions on forecast quality. Our results suggest that a meta-ensemble of statistical and mechanistic methods has better overall accuracy than the individual methods. Supplementing surveillance data with proxy estimates generally improves the quality of forecasts and transient reporting errors degrade the performance of all three approaches considerably. The improvement in quality from ad hoc and post-forecast changes suggests that domain experts continue to possess information that is not being sufficiently captured by current forecasting approaches.
Both stiff and compliant: morphological and biomechanical adaptations of stick insect antennae for tactile exploration
Authors: Rajabi H. , Shafiei A. , Darvizeh A. , Gorb S. N. , Dürr V. , Dirks J.-H.
Published: July 2018

Active tactile exploration behaviour is constrained to a large extent by the morphological and biomechanical properties of the animal's somatosensory system. In the model organismCarausius morosus, the main tactile sensory organs are long, thin, seemingly delicate, but very robust antennae. Previous studies have shown that these antennae are compliant under contact, yet stiff enough to maintain a straight shape during active exploration. Overcritical damping of the flagellum, on the other hand, allows for a rapid return to the straight shape after release of contact. Which roles do the morphological and biomechanical adaptations of the flagellum play in determining these special mechanical properties? To investigate this question, we used a combination of biomechanical experiments and numerical modelling. A set of four finite-element (FE) model variants was derived to investigate the effect of the distinct geometrical and material properties of the flagellum on its static (bending) and dynamic (damping) characteristics. The results of our numerical simulations show that the tapered shape of the flagellum had the strongest influence on its static biomechanical behaviour. The annulated structure and thickness gradient affected the deformability of the flagellum to a lesser degree. The inner endocuticle layer of the flagellum was confirmed to be essential for explaining the strongly damped return behaviour of the antenna. By highlighting the significance of two out of the four main structural features of the insect flagellum, our study provides a basis for mechanical design of biomimetic touch sensors tuned to become maximally flexible while quickly resuming a straight shape after contact.
An analytical approach for quantifying the influence of nanoparticle polydispersity on cellular delivered dose
Authors: Johnston Stuart T. , Faria Matthew , Crampin Edmund J.
Published: July 2018

Nanoparticles provide a promising approach for the targeted delivery of therapeutic, diagnostic and imaging agents in the body. However, it is not yet fully understood how the physico-chemical properties of the nanoparticles influence cellular association and uptake. Cellular association experiments are routinely performed in an effort to determine how nanoparticle properties impact the rate of nanoparticle–cell association. To compare experiments in a meaningful manner, the association data must be normalized by the amount of nanoparticles that arrive at the cells, a measure referred to as the delivered dose. The delivered dose is calculated from a model of nanoparticle transport through fluid. A standard assumption is that all nanoparticles within the population are monodisperse, namely the nanoparticles have the same physico-chemical properties. We present a semi-analytic solution to a modified model of nanoparticle transport that allows for the nanoparticle population to be polydisperse. This solution allows us to efficiently analyse the influence of polydispersity on the delivered dose. Combining characterization data obtained from a range of commonly used nanoparticles and our model, we find that the delivered dose changes by more than a factor of 2 if realistic amounts of polydispersity are considered.
Who are you, subdistal appendages of centriole?
Authors: Uzbekov Rustem , Alieva Irina
Published: July 2018

This review summarizes data that assign morphological, biochemical and functional characteristics of two types of structures that are associated with centrioles: distal appendages and subdistal appendages. The description of centriole subdistal appendages is often a matter of confusion, both due to the numerous names used to describe these structures and because of their variability among species and cell types. Thus, we have summarized our current knowledge in this review. We conclude that distal appendages and subdistal appendages are fundamentally different in composition and function in the cell. While in centrioles there are always nine distal appendages, the number of subdistal appendages can vary depending on the type of cells and their functional state.
Elastic waves in periodically heterogeneous two-dimensional media: locally periodic and anti-periodic modes
Authors: Andrianov Igor V. , Danishevskyy Vladyslav V. , Rogerson Graham
Published: July 2018

Propagation of anti-plane waves through a discrete square lattice and through a continuous fibrous medium is studied. In the long-wave limit, for periodically heterogeneous structures the solution can be periodic or anti-periodic across the unit cell. It is shown that combining periodicity and anti-periodicity conditions in different directions of the translational symmetry allows one to detect different types of modes that do not arise in the purely periodic case. Such modes may be interpreted as counterparts of non-classical waves appearing in phenomenological theories. Dispersion diagrams of the discrete square lattice are evaluated in a closed analytical from. Dispersion properties of the fibrous medium are determined using Floquet–Bloch theory and Fourier series approximations. Influence of a viscous damping is taken into account.