bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-floor laboratory transportation technologies based on intelligent mobile robots
Authors: Thurow Kerstin , Zhang Lei , Liu Hui , Junginger Steffen , Stoll Norbert , Huang Jiahao
Published: January 2019

Transportation technologies for mobile robots include indoor navigation, intelligent collision avoidance and target manipulation. This paper discusses the research process and development of these interrelated technologies. An efficient multi-floor laboratory transportation system for mobile robots developed by the group at the Center for Life Science Automation (CELISCA) is then introduced. This system is integrated with the multi-floor navigation and intelligent collision avoidance systems, as well as a labware manipulation system. A multi-floor navigation technology is proposed, comprising sub-systems for mapping and localization, path planning, door control and elevator operation. Based on human–robot interaction technology, a collision avoidance system is proposed that improves the navigation of the robots and ensures the safety of the transportation process. Grasping and placing operation technologies using the dual arms of the robots are investigated and integrated into the multi-floor transportation system. The proposed transportation system is installed on the H20 mobile robots and tested at the CELISCA laboratory. The results show that the proposed system can ensure the mobile robots are successful when performing multi-floor laboratory transportation tasks.
Sinus Wounds Management
Authors: Jiang Zheng-Ying , Liu Ming-Zhuo , Fu Zhong-Hua , Liao Xin-Cheng , Guo Guang-Hua
Published: January 2019

With aging populations and the increased incidence of cerebrovascular disease, diabetes, and other diseases, more and more patients suffer from pressure injuries. Pressure injuries are often difficult to heal because of the presence of sinus tracts, which make it difficult to clean and change dressings. Sinus wounds are common in patients with pressure injuries, but also occur after abdominal wall incision and in patients who have experienced a physical trauma that created a wound. It is difficult for clinicians to observe, evaluate, and repair sinus wounds because of the small surface defect and large and deep basement of each wound. This article reviews existing assessment methods and treatments for sinus wounds and proposes a new evaluation method and treatment (three-dimensional reconstruction and endoscopic techniques) to further improve treatment and provide better quality of care for patients with this type of wound.
Recruiting and Training a Health Professions Workforce to Meet the Needs of Tomorrow’s Health Care System
Authors: Raffoul Melanie , Bartlett-Esquilant Gillian , Phillips Robert L.
Published: January 2019

The quality of any health care system depends on the caliber, enthusiasm, and diversity of the workforce. Yet, workforce research often focuses on the number and type of health professionals needed and anticipated shortages compared with anticipated needs. These projections do not address whether the workforce will have the requisite social, intellectual, cultural, and emotional capital needed to deliver care in an increasingly complex health care system.

Building a workforce that can deliver care in such a system begins by recruiting individuals with the requisite knowledge, skills, and attributes. To address this and other workforce needs, the authors argue that health professions education programs must make purposeful changes to their admissions criteria, such as focusing on emotional intelligence and diversity and recruiting students from the communities where they will return to work; partner with communities; ensure that accreditation systems support these goals of fostering diversity; recruit students who can bridge the gap between public health and health care; and invest in health professions education research.

In this article, they contemplate how health professions education programs can recruit and educate talented health professionals to create a high-performing workforce that is capable of serving in the complex health care system of tomorrow. They provide examples of successful programs to highlight the potential effects of their recommendations.
Debriefing for the Transfer of Learning: The Importance of Context
Authors: Rivière Etienne , Jaffrelot Morgan , Jouquan Jean , Chiniara Gilles
Published: January 2019

The advent of simulation-based education has caused a renewed interest in feedback and debriefing. However, little attention has been given to the issue of transfer of learning from the simulation environment to real-life and novel situations. In this article, the authors discuss the importance of context in learning, based on the frameworks of analogical transfer and situated cognition, and the limitations that context imposes on transfer. They suggest debriefing strategies to improve transfer of learning: positioning the lived situation within its family of situations and implementing the metacognitive strategies of contextualizing, decontextualizing, and recontextualizing. In contextualization, the learners’ actions, cognitive processes, and frames of reference are discussed within the context of the lived experience, and their mental representation of the situation and context is explored. In decontextualization, the underlying abstract principles are extracted without reference to the situation, and in recontextualization, those principles are adapted and applied to new situations and to the real-life counterpart. This requires that the surface and deep features that characterize the lived situation be previously compared and contrasted with those of the same situation with hypothetical scenarios (“what if”), of new situations within the same family of situations, of the prototype situation, and of real-life situations. These strategies are integrated into a cyclical contextualization, decontextualization, and recontextualization model to enhance debriefing.
Transitioning From Volume to Value: Lessons Learned From the Dissolution of a Population Health Partnership
Authors: Halvorson Stephanie A.C. , Tanski Mary , Milligan Lee , Yackel Thomas
Published: January 2019

In 2017, the authors published an article describing the experiences of Oregon Health & Science University (OHSU) as it adapted to new challenges of changing payment models, the imperative to manage the health of populations, and the desire to compete for statewide contracts. The authors described Propel Health, a multi-institution partnership created in 2013 to deliver the tools, methods, and support necessary for population health management. In the ensuing two years there were considerable changes to the structure and mission of Propel Health, ultimately resulting in its dissolution in January 2018. Using the organizational framework from the original publication, this article shares a number of lessons learned with other academic medical centers as they make the journey toward value-based care and population health management. Examples of lessons learned include ensuring that clinical and administrative leadership are aligned and that shared partnership goals are not eclipsed by local strategic needs. The potential for shared data remains a powerful motivation to partner; however, technology integration can be costly and complex. Once data are available, the ability to respond quickly is a key competency. Understanding individual sites’ needs and capabilities is critical before embarking on shared clinical programs. Best practices from industry-specific experts should be employed. Lastly, it is essential for partners to determine how shared gains/losses will be attributed, and how aggressively risk should be required. Next steps for OHSU, including new, local partnerships, are shared.
Clinical Practice Guidelines for Pain Management in Acute Musculoskeletal Injury
Authors: Hsu Joseph R. , Mir Hassan , Wally Meghan K. , Seymour Rachel B. ,   the Orthopaedic Trauma Association Musculoskeletal Pain Task Force
Published: January 2019

Purpose:

We aimed to produce comprehensive guidelines and recommendations that can be utilized by orthopaedic practices as well as other specialties to improve the management of acute pain following musculoskeletal injury.

Methods:

A panel of 15 members with expertise in orthopaedic trauma, pain management, or both was convened to review the literature and develop recommendations on acute musculoskeletal pain management. The methods described by the Grading of Recommendations Assessment, Development, and Evaluation Working Group were applied to each recommendation. The guideline was submitted to the Orthopaedic Trauma Association (OTA) for review and was approved on October 16, 2018.

Results:

We present evidence-based best practice recommendations and pain medication recommendations with the hope that they can be utilized by orthopaedic practices as well as other specialties to improve the management of acute pain following musculoskeletal injury. Recommendations are presented regarding pain management, cognitive strategies, physical strategies, strategies for patients on long term opioids at presentation, and system implementation strategies. We recommend the use of multimodal analgesia, prescribing the lowest effective immediate-release opioid for the shortest period possible, and considering regional anesthesia. We also recommend connecting patients to psychosocial interventions as indicated and considering anxiety reduction strategies such as aromatherapy. Finally, we also recommend physical strategies including ice, elevation, and transcutaneous electrical stimulation. Prescribing for patients on long term opioids at presentation should be limited to one prescriber. Both pain and sedation should be assessed regularly for inpatients with short, validated tools. Finally, the group supports querying the relevant regional and state prescription drug monitoring program, development of clinical decision support, opioid education efforts for prescribers and patients, and implementing a department or organization pain medication prescribing strategy or policy.

Conclusions:

Balancing comfort and patient safety following acute musculoskeletal injury is possible when utilizing a true multimodal approach including cognitive, physical, and pharmaceutical strategies. In this guideline, we attempt to provide practical, evidence-based guidance for clinicians in both the operative and non-operative settings to address acute pain from musculoskeletal injury. We also organized and graded the evidence to both support recommendations and identify gap areas for future research.
Forefoot Supination and Medial Column Instability in the Setting of AAFD: The Role of the Medial Column
Authors: Abyar Eildar , O’Daly Andrés E. , Shah Ashish B. , Johnson Michael D.
Published: January 2019

Several variables may contribute to adult-acquired flatfoot deformity, one such variable is the medial column of the foot, which commonly manifest as forefoot varus or supination. The medial column is subjected to considerable loads during gait, and under normal conditions provides dynamic stability during the stance phase of gait. Pathology occurring along the medial column and forefoot can disrupt normal foot mechanics and lead to flatfoot deformity. A careful history and examination can diagnose dysfunction relating to the medial column and forefoot. Specifically, first tarsometatarsal dysfunction can result in malalignment, and loss of first ray stability. It is important to consider all potential sources of medial column insufficiency since dysfunction can occur at any point along its course. Stabilization and joint-sparing techniques may be used to correct multiplanar malalignment of the first tarsometatarsal joint, and offers a powerful means of preserving foot mechanics.
Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*
Authors: Gleeson Patrick J. , Crippa Ilaria Alice , Mongkolpun Wasineenart , Cavicchi Federica Zama , Van Meerhaeghe Tess , Brimioulle Serge , Taccone Fabio Silvio , Vincent Jean-Louis , Creteur Jacques
Published: January 2019

Objectives:

To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice.

Design:

Prospective observational study.

Setting:

Single-center, mixed medical-surgical ICU in Europe.

Patients:

Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin.

Interventions:

Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison.

Measurements and Main Results:

One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± sd, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = –0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = –0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± sd 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (–32 ± 26 μU/timepoint vs +92 ± 57 μU/timepoint p = 0.03; mean ± sem), but not for lactate (–0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17).

Conclusions:

In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.
Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?
Authors: De Bruyn Pauline , Van Gestel Dirk , Ost Piet , Kruse Vibeke , Brochez Lieve , Van Vlierberghe Hans , Devresse Arnaud , del Marmol Véronique , Le Moine Alain , Aspeslagh Sandrine
Published: January 2019

Purpose of review

Checkpoint inhibitors (CPIs) provide impressive response rates among immunocompetent patients with various solid tumors. So far, organ transplant recipients have been excluded from clinical studies due to the putative risk of allograft rejection however 48 cases of liver and renal transplant patients treated with CPI were already described in literature.

Recent findings

Here we discuss 19 cases of liver and 29 cases of renal transplant patients who received CPI for advanced cancer. Disease control rate [stable disease, complete response (CR) and partial response (PR) together] was 35% (21% for liver and 45% for kidney transplant patients). Graft rejection was seen in 37% of liver and 45% and kidney transplant patients. Significantly, our analysis shows that an ‘ideal’ response occurs in 21% of all patients (antitumor response accompanied with durable graft tolerance).

We believe that transplant patients can be treated with CPI in a controlled setting and for well informed patients. To obtain a durable antitumor immune response while avoiding rejection, to be able to adjust immunosuppression and to have the opportunity to develop biomarkers for tumor response and transplant rejection, these patients should be treated according to a clinical care path or a prospective clinical trial.
A Collaboration Between Government and the Continuing Education Community Tackles the Opioid Crisis: Lessons Learned and Future Opportunities
Authors: Kahn Norman , Chappell Kathy , Regnier Kate , Travlos Dimitra V. , Auth Doris
Published: January 2019

In 2016, 116 people died each day from opioid-related drug overdoses and in 2017, the Department of Health and Human Services declared the opioid crisis a public health emergency. During the preceding years, the continuing education (CE) accreditors in the health professions identified a need for a strategic, coordinated effort that would involve an interprofessional coalition of multiple stakeholders to respond to this emerging public health challenge. The Conjoint Committee on Continuing Education, a national coalition of organizations in the professions of medicine, nursing, dentistry, pharmacy, and physician assistants, stepped up to assume a leadership position. To address the scope of safety issues involved in opioids, the US Food and Drug Administration required that extended-release and long-acting opioid analgesic product manufacturers make training available to prescribers of their products and recommended that the training should be conducted by accredited, independent CE providers. CE accreditors in the health professions initiated an unprecedented collaboration that leveraged the accredited CE community to deliver prescriber education as part of the Food and Drug Administration Opioid Analgesics Risk Evaluation and Mitigation Strategy. This article describes the history of this interprofessional collaboration including lessons learned and opportunities for future collaboration to address public health issues.
Nurturing the Virtues: Upholding Professionalism in the Midst of Busy Medical Practice
Authors: Bäckryd Emmanuel
Published: January 2019

Tom L. Beauchamp and James F. Childress' (B&C) book Principles of Biomedical Ethics is well known for its four-principle approach to biomedical ethics. However, the authors also emphasize the importance of the virtues of health care personnel. After a short overview of virtue ethics, the five “focal virtues” described by B&C are discussed and applied to a chronic pain example. The question of how virtues are learned in the health care setting is addressed, and it is argued that virtues such as the ones defended by B&C are acquired when health care personnel are socialized in an environment dedicated to the continuous upholding of practices that aim at the telos of medicine. Viewed from this perspective, professional isolation can be considered to be dangerous; the upholding of medical professionalism throughout a whole career largely presupposing the existence of a community where virtues relevant to the practice of medicine are embodied and kept alive. The concept of professional socialization is important in that respect. Finally, some potential general implications of this view for continuing professional development are proposed.
A Phase II Study Evaluating Bone Marrow-Sparing, Image-guided Pelvic Intensity-Modulated Radiotherapy (IMRT) With Cesium-131 Brachytherapy Boost, Adjuvant Chemotherapy, and Long-Term Hormonal Ablation in Patients With High Risk, Nonmetastatic Prostate Cancer
Authors: Rice Stephanie R. , Olexa Gloribel , Hussain Arif , Mannuel Heather , Naslund Michael J. , Amin Pradip , Kwok Young
Published: January 2019

Purpose/Objective(s):

Management of localized high-risk prostate cancer remains challenging. At our institution we performed a prospective phase II study of 2 years of androgen deprivation therapy (ADT), pelvic radiation, Cesium (Cs)-131 brachytherapy boost, and adjuvant docetaxel in high risk, localized prostate cancer with a primary endpoint of 3-year disease-free survival.

Materials/Methods:

Acute/chronic hematologic, gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0/RTOG-EORTC criteria, respectively. Actuarial biochemical recurrence free survival (bRFS), bRFSdisease free survival (DFS) and overall survival (OS) were calculated. Patients had a median age of 62 years (range, 45 to 82), median Gleason score 8 (74% Gleason 8-10), median PSA of 11.2 (range, 2.8 to 96), and 47% cT2-T3a stage disease. Androgen deprivation was given for 2 years, 45 Gy whole-pelvis IMRT was followed by an 85 Gy Cs-131 boost to the prostate gland, and adjuvant docetaxel was given for 4 cycles.

Results:

In total 38 patients enrolled from 2006 to 2014, with 82% completing protocol specified treatment, and 84.2% completing 4 cycles of docetaxel. Median follow-up for the entire and alive cohorts were 44 months and 58 months (range, 3.4 to 118), respectively. Acute grade ≥2 GI and GU toxicity rates were 18.4% and 23.7%, respectively. Chronic grade ≥2 GI and GU toxicity rates were 2.6% and 2.6%, respectively. Twelve patients (31.6%) developed grade 4 hematologic toxicity, with no grade 5 toxicity. The 5-year DFS, bRFS and OS rates were 74.1%, 86.0%, and 80.3%, respectively.

Conclusions:

This aggressive pilot multimodal approach appears to be safe and well-tolerated, providing disease control in a significant proportion of patients with particularly high-risk prostate cancer.
Satellite and In-Transit Metastatic Disease in Melanoma Skin Cancer: A Retrospective Review of Disease Presentation, Treatment, and Outcomes
Authors: Bann Darrin V. , Chaikhoutdinov Irina , Zhu Junjia , Andrews Genevieve
Published: January 2019

BACKGROUND

Satellitosis and in-transit metastases (SITM) are uncommon in cutaneous melanoma and are associated with poor prognosis. However, the disease- and treatment-specific variables that predict outcomes among patients with SITM are poorly defined.

OBJECTIVE

To identify factors that predict prognosis among patients with SITM.

MATERIALS AND METHODS

Retrospective chart review of patients treated for melanoma at a large academic medical center in central Pennsylvania between 2000 and 2012. Patients with pathology reports containing “satellite lesions” or “in-transit metastases” were selected for analysis. Data were collected regarding tumor stage, the timing of SITM discovery, treatment, recurrence-free survival after SITM discovery, and overall survival (OS).

RESULTS

We identified SITM in 32 (1.9%) of 1,650 patients with pathology-diagnosed melanoma over the study period. Reduced recurrence-free survival after SITM discovery was associated with higher pathologic stage, metastatic disease, lymph node dissection, and use of adjuvant chemotherapy. Reduced OS was associated with higher T, N, M, and overall prognostic stage; positive surgical margins; disease recurrence; and SITM on initial presentation.

CONCLUSION

Our data support previous findings that higher stage disease confers a worse prognosis among patients with SITM. Patients with SITM on initial presentation had worse outcomes, suggesting SITM is indicative of more aggressive disease.
Influence of aversive stimulation on haloperidol-induced catalepsy in rats
Authors: Barroca Nayara C.B. , Guarda Mariana D. , da Silva Naiara T. , Colombo Ana C. , Reimer Adriano E. , Brandão Marcus L. , de Oliveira Amanda R.
Published: January 2019

Catalepsy – an immobile state in which individuals fail to change imposed postures – can be induced by haloperidol. In rats, the pattern of haloperidol-induced catalepsy is very similar to that observed in Parkinson’s disease (PD). As some PD symptoms seem to depend on the patient’s emotional state, and as anxiety disorders are common in PD, it is possible that the central mechanisms regulating emotional and cataleptic states interplay. Previously, we showed that haloperidol impaired contextual-induced alarm calls in rats, without affecting footshock-evoked calls. Here, we evaluated the influence of distinct aversive stimulations on the haloperidol-induced catalepsy. First, male Wistar rats were subjected to catalepsy tests to establish a baseline state after haloperidol or saline administration. Next, distinct cohorts were exposed to open-field; elevated plus-maze; open-arm confinement; inescapable footshocks; contextual conditioned fear; or corticosterone administration. Subsequently, catalepsy tests were performed again. Haloperidol-induced catalepsy was verified in all drug-treated animals. Exposure to open-field, elevated plus-maze, open-arm confinement, footshocks, or administration of corticosterone had no significant effect on haloperidol-induced catalepsy. Contextual conditioned fear, which is supposed to promote a more intense fear, increased catalepsy over time. Our findings suggest that only specific defensive circuitries modulate the nigrostriatal system mediating the haloperidol-induced cataleptic state.
A Short Communication: Lamotrigine Levels in Milk, Mothers, and Breastfed Infants During the First Postnatal Month
Authors: Kacirova Ivana , Grundmann Milan , Brozmanova Hana
Published: January 2019

Background:

Lamotrigine has become the most frequently prescribed drug in the treatment of pregnant women with epilepsy. Although some relevant studies have found a wide milk/maternal serum as well as infant/maternal serum concentration ratio, different infant ages at the time of sampling and small number of patients preclude comparison. The aim of this study was to provide a consistent evaluation.

Methods:

Data of 43 nursing women treated by lamotrigine were evaluated retrospectively. The authors followed the transport of lamotrigine during the first postnatal month from mothers to breastfed infants through maternal milk between the years 2002 and 2017.

Results:

Lamotrigine concentrations varied from 1.1 to 14.9 mg/L in the maternal serum, from <0.66 to 9.1 mg/L in the milk and between <0.66 and 6.9 mg/L in the infant serum. The milk/maternal serum concentration ratio ranged from <0.18 to 0.74 and the infant/maternal serum concentration ratio measured between <0.15 and 0.74. Highly significant correlations were found between milk and maternal serum levels and between infant serum levels and milk, maternal serum levels, lamotrigine daily dose, and also maternal dose related to the body weight.

Conclusions:

The authors confirmed the wide range of the milk/maternal serum concentration ratio and the infant/maternal serum concentration ratio. Although the degree of lamotrigine exposure to the breastfed infants was smaller than during gestation, 16% of the infant serum levels measured were within the therapeutic range used for the general epileptic population. Lamotrigine concentration monitoring in breastfed infant, in our opinion, is the most relevant aspect for the analysis of actual lamotrigine exposure in infants, especially in those with clinical symptoms.
CAR T Cells: A Snapshot on the Growing Options to Design a CAR
Authors: Holzinger Astrid , Abken Hinrich
Published: January 2019

Adoptive cell therapy of malignant diseases with chimeric antigen receptor (CAR) modified T cells rapidly advanced from pre‐clinical models to commercial approvals within 2 decades. CARs redirect patient's T cells towards cancer cells and activate the engineered cells for a cytolytic attack resulting in the destruction of the cognate target cell. CAR T cells have demonstrated their powerful capacities in inducing complete and lasting remissions of leukemia/lymphoma in an increasing number of trials worldwide. Since the early 90's, the design of CARs went through various steps of optimization until the very recent developments which include CARs with logic gating in the recognition of antigen patterns on target cells and TRUCKs with a target recognition induced delivery of immune modulating agents. Here we review the generations in CAR design, the impact of specific modifications, the strategies to improve the safety of CAR T cell therapy, and the challenges to adapt the CAR design for broader applications.
Impact of Nanostructured Lipid Carriers as an Artificial Tear Film in a Rabbit Evaporative Dry Eye Model
Authors: Niamprem Pattravee , Teapavarapruk Pronnarin , Srinivas Sangly P. , Tiyaboonchai Waree
Published: January 2019

Purpose:

To characterize formulations of nanostructured lipid carriers (NLCs) as an artificial tear film and evaluate their efficacy in protecting the ocular surface epithelial cells from desiccating stress in vivo.

Methods:

The physicochemical properties of NLCs, produced with components similar to the tear film such as phosphatidylcholine and squalene, were determined. In vitro cytotoxicity of NLCs was evaluated by a short-time exposure test in porcine corneal epithelial cells using a methyl thiazol diphenyl-tetrazolium bromide assay. The residence time of NLCs in rabbit eyes and the efficacy of NLCs eye drops in protecting the rabbit corneal epithelium from desiccating stress were assessed.

Results:

Nanosized NLCs with a mean size of ∼39 ± 5 nm and a zeta potential of −30 mV could be produced and formulated into eye drop with a pH of 6.90 ± 0.01, osmolarity of 273 ± 1 mOsm/L, and surface tension of 39 ± 1 mN/m (for air interface). Eye drop formulations of NLCs were nontoxic to porcine corneal epithelial cells. NLCs drops showed higher ocular surface retention and formed a stable corneal film compared with a saline solution. Moreover, NLCs eye drops showed greater efficacy in protecting the corneal surface against desiccating stress compared with a polymer-based commercial artificial tear.

Conclusions:

NLCs eye drops are biocompatible in rabbit eyes and show potential as a tear replacement vehicle for the treatment of dry eye disease.
Comparative Functional Outcomes After Corneal Crosslinking Using Standard, Accelerated, and Accelerated With Higher Total Fluence Protocols
Authors: Lang Paul Z. , Hafezi Nikki L. , Khandelwal Sumitra S. , Torres-Netto Emilio A. , Hafezi Farhad , Randleman J. Bradley
Published: January 2019

Purpose:

To compare the relative 12-month corneal crosslinking (CXL) functional outcomes using standard protocol and accelerated protocols in patients with progressive keratoconus.

Methods:

CXL was performed using 3 epithelium-off protocols: standard [3 mW/cm2 for 30 minutes, 5.4 J/cm2 (S3/30-CXL)], accelerated with equivalent total irradiance [9 mW/cm2 for 10 minutes, 5.4 J/cm2 (A9/10-CXL)], and accelerated with increased total irradiance [30 mW/cm2 for 4 minutes, 7.2 J/cm2 (A30/4-CXL)]. Efficacy measurements were evaluated 12 months after treatment with Scheimpflug imaging (Pentacam HR) and included change in maximum keratometry (K Max), corrected distance visual acuity (CDVA), other keratometric variables, pachymetry, keratoconus indices, astigmatism, asphericity, manifest refraction, and higher order aberrations.

Results:

Ninety-three eyes (67 patients) were evaluated: 35 eyes (26 patients) with S3/30-CXL, 29 eyes (19 patients) with A9/10-CXL, and 29 eyes (22 patients) with A30/4-CXL. Mean ∆K Max was −1.53 ± 2.1 diopter (D) for S3/30-CXL, −0.71 ± 1.3 D for A9/10-CXL, and −0.70 ± 2.3 D for A30/4-CXL (P = 0.37). Mean ∆CDVA(logMAR) was −0.18 ± 0.2 for S3/30-CXL, −0.13 ± 0.2 for A9/10-CXL, and −0.18 ± 0.2 for A30/4-CXL (P = 0.79). ∆K Mean (r = −0.29 to −0.46), anterior asphericity (r = −0.34 to −0.40), and central keratoconus index (r = −0.18 to −0.38) best correlated with ∆CDVA. S3/30-CXL had greater changes in index of surface variance, index of vertical asymmetry, keratoconus index, and regularization index compared to A9/10-CXL and A30/4-CXL. There were no other differences between protocols.

Conclusions:

All 3 protocols showed improvements in K Max, CDVA, and other variables, with similar functional outcomes for each despite greater change in keratoconus indices after S3/30-CXL. Correlations between change in measured variables and CDVA were poor overall; however, K Mean, central keratoconus index, and anterior asphericity were better correlated with CDVA than K Max.
Congenital Refractory Glaucoma: A New Ophthalmic Association of Kabuki Syndrome and its Management With Glaucoma Drainage Devices
Authors: Bravetti Giorgio E. , Gillmann Kevin , Mansouri Kaweh , Mermoud André
Published: January 2019

Introduction:

Kabuki syndrome (KS) is a rare congenital and polymalformative condition, traditionally associated with mental retardation, unusual facial features, and skeletal abnormalities. We hereby describe a case of bilateral congenital glaucoma associated with MLL2-mutation KS. To the best of our knowledge, this is the first association of KS with congenital glaucoma.

Case Report:

The patient was a 3-year-old male of North African ethnicity diagnosed with KS and bilateral congenital glaucoma at the age of 3 months and the first child of a nonconsanguineous healthy couple, with no known genetic conditions within the family. The patient was referred to our tertiary glaucoma center with uncontrollable intraocular pressures between 50 and 60 mm Hg in both eyes. Past ophthalmic history included bilateral trabeculectomies and right retinal detachment with phthisis bulbi. We performed left lensectomy combined with Baerveldt tube insertion in the vitreous cavity, revealing extensive posterior synechiae. Postoperatively, he developed intense inflammation with fibrin and vitreous strand formation, requiring subsequent surgeries and subconjunctival injections of betamethasone. Despite these complications, IOP stabilized between 3 and 6 mm Hg.

Discussion:

This case confirms congenital glaucoma as a rare association of KS, and highlights the potential high-risk nature of such cases. In our opinion, the presence of high levels of inflammation perioperatively and postoperatively is an indication for primary glaucoma drainage device surgery given the high risk of bleb scarring resulting in recurrent surgical revisions. In view of these observations, we also advocate the use of intensive postoperative anti-inflammatory therapy.
Vision Loss After Glaucoma Surgery: Progressive Macular Thinning as a Sign of Snuff-Out Phenomenon
Authors: Mohammadzadeh Vahid , Galian Katrina , Martinyan Jack , Nouri-Mahdavi Kouros
Published: January 2019

We herein report 2 eyes with significant loss of vision after glaucoma filtering surgery that was accompanied by progressive macular thinning detected on macular optical coherence tomography imaging. The findings provide evidence that progressive retinal ganglion cell loss is one of the causes of visual loss after uncomplicated glaucoma surgery.
Adenosine A3 receptor activation inhibits pronociceptive N-type Ca2+ currents and cell excitability in dorsal root ganglion neurons
Authors: Coppi Elisabetta , Cherchi Federica , Fusco Irene , Failli Paola , Vona Alessia , Dettori Ilaria , Gaviano Lisa , Lucarini Elena , Jacobson Kenneth A. , Tosh Dilip K. , Salvemini Daniela , Ghelardini Carla , Pedata Felicita , Di Cesare Mannelli Lorenzo , Pugliese Anna Maria
Published: January 2019

Recently, studies have focused on the antihyperalgesic activity of the A3 adenosine receptor (A3AR) in several chronic pain models, but the cellular and molecular basis of this effect is still unknown. Here, we investigated the expression and functional effects of A3AR on the excitability of small- to medium-sized, capsaicin-sensitive, dorsal root ganglion (DRG) neurons isolated from 3- to 4-week-old rats. Real-time quantitative polymerase chain reaction experiments and immunofluorescence analysis revealed A3AR expression in DRG neurons. Patch-clamp experiments demonstrated that 2 distinct A3AR agonists, Cl-IB-MECA and the highly selective MRS5980, inhibited Ca2+-activated K+ (KCa) currents evoked by a voltage-ramp protocol. This effect was dependent on a reduction in Ca2+ influx via N-type voltage-dependent Ca2+ channels, as Cl-IB-MECA–induced inhibition was sensitive to the N-type blocker PD173212 but not to the L-type blocker, lacidipine. The endogenous agonist adenosine also reduced N-type Ca2+ currents, and its effect was inhibited by 56% in the presence of A3AR antagonist MRS1523, demonstrating that the majority of adenosine's effect is mediated by this receptor subtype. Current-clamp recordings demonstrated that neuronal firing of rat DRG neurons was also significantly reduced by A3AR activation in a MRS1523-sensitive but PD173212-insensitive manner. Intracellular Ca2+ measurements confirmed the inhibitory role of A3AR on DRG neuronal firing. We conclude that pain-relieving effects observed on A3AR activation could be mediated through N-type Ca2+ channel block and action potential inhibition as independent mechanisms in isolated rat DRG neurons. These findings support A3AR-based therapy as a viable approach to alleviate pain in different pathologies.
Pain-related nucleus accumbens function: modulation by reward and sleep disruption
Authors: Seminowicz David A. , Remeniuk Bethany , Krimmel Samuel R. , Smith Michael T. , Barrett Frederick S. , Wulff Andreas B. , Furman Andrew J. , Geuter Stephan , Lindquist Martin A. , Irwin Michael R. , Finan Patrick H.
Published: January 2019

The nucleus accumbens (NAc) has been implicated in sleep, reward, and pain modulation, but the relationship between these functional roles is unclear. This study aimed to determine whether NAc function at the onset and offset of a noxious thermal stimulus is enhanced by rewarding music, and whether that effect is reversed by experimental sleep disruption. Twenty-one healthy subjects underwent functional magnetic resonance imaging scans on 2 separate days after both uninterrupted sleep and experimental sleep disruption. During functional magnetic resonance imaging scans, participants experienced noxious stimulation while listening to individualized rewarding or neutral music. Behavioral results revealed that rewarding music significantly reduced pain intensity compared with neutral music, and disrupted sleep was associated with decreased pain intensity in the context of listening to music. In whole-brain family-wise error cluster-corrected analysis, the NAc was activated at pain onset, but not during tonic pain or at pain offset. Sleep disruption attenuated NAc activation at pain onset and during tonic pain. Rewarding music altered NAc connectivity with key nodes of the corticostriatal circuits during pain onset. Sleep disruption increased reward-related connectivity between the NAc and the anterior midcingulate cortex at pain onset. This study thus indicates that experimental sleep disruption modulates NAc function during the onset of pain in a manner that may be conditional on the presence of competing reward-related stimuli. These findings point to potential mechanisms for the interaction between sleep, reward, and pain, and suggest that sleep disruption affects both the detection and processing of aversive stimuli that may have important implications for chronic pain.
Trajectories of sickness absence and disability pension before and after opioid initiation for noncancer pain: a 10-year population-based study
Authors: Lalic Samanta , Bell J. Simon , Gyllensten Hanna , Gisev Natasa , Friberg Emilie , Ilomaki Jenni , Sluggett Janet K. , Mittendorfer-Rutz Ellenor , Alexanderson Kristina
Published: January 2019

Chronic noncancer pain is a leading cause of sickness absence (SA) and disability pension (DP). The objectives of this study were to identify trajectories of SA/DP before and after strong and weak opioid initiation for noncancer pain and the factors associated with these trajectories. A longitudinal population-based study of 201,641 people (24-59 years) without cancer who initiated opioid analgesics in 2009 in Sweden was conducted. Trajectories of net annual SA/DP days in the 5 years before/after opioid initiation were estimated with group-based trajectory modelling. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with trajectory groups. Among the 6.9% of people initiating strong opioids, 12.5% had persistent high SA/DP (estimated 320 days/year) before and after opioid initiation and 72.9% had persistent low/minimum SA/DP (estimated 30 days/year). Approximately 8.6% of people had increasing SA/DP, and 6.1% had decreasing SA/DP after opioid initiation, although this seemed to reflect continuation of preinitiation patterns. Trajectories were similar at lower SA/DP days/year among those initiating weak opioids. Persistent high SA/DP among strong opioid initiators were associated with ≥5 comorbidities (OR = 8.72, 95% CI 5.61-13.56), ≤9 years of education (OR = 5.83, 95% CI 4.84-7.03), and previous use of antidepressants (OR = 4.57, 95% CI 3.89-5.37) and antipsychotics (OR = 4.49, 95% CI 2.93-6.88). Three-quarters of people initiating opioids for noncancer pain had persistent low/minimum levels of SA/DP 5 years before and after initiation. Increasing and decreasing SA/DP after opioid initiation seemed to reflect a continuation of preinitiation patterns. Our findings highlight the complex range of sociodemographic and medication-related factors associated with persistent SA/DP.
Olfactory Dysfunction in Aging African American and Caucasian Men With HIV: A Pilot Study
Authors: Vance David E. , Cody Shameka L. , Nicholson Chance , Cheatwood John , Morrison Shannon , Fazeli Pariya L.
Published: January 2019

As people age with HIV, olfactory dysfunctions may become more pronounced, especially for African Americans who are predisposed to declines in olfaction. In this cross-sectional study, 34 middle-age and older African American and 17 Caucasian men living with HIV were administered two objective olfactory measures (UPSIT). In the Smell Threshold Test, compared to the HIV-negative age norms, adults living with HIV were significantly less able to detect a lower threshold smell. In the University of Pennsylvania Smell Identification Test, compared to the HIV-negative age norms, adults living with HIV were significantly less able to correctly identify odors; furthermore, using such norms, African Americans with HIV were less likely to correctly identify odors compared to Caucasians with HIV. Since the literature indicates that African Americans have a stronger attraction for salty and sweet foods, such olfactory dysfunction may contribute to poor eating habits, potentially predisposing this population to additional health problems.
Insurance Status and Access to Sexual Health Services Among At-Risk Men: A Qualitative Study
Authors: Sowemimo-Coker Genoviva , Lee Alice J. , Montgomery Madeline C. , Nunn Amy S. , van den Berg Jacob J. , Chan Philip A.
Published: January 2019

Our objective was to evaluate the impact of insurance coverage on access to sexual health services among at-risk men. Data were collected from Hispanic/Latino and non-Hispanic White male patients at a publicly funded sexually transmitted disease clinic in a Medicaid expansion state from February to July 2017, using in-depth, semistructured interviews. A coding scheme was applied to interview transcripts with iterative revisions until a final coding scheme was achieved. Data were analyzed using Nvivo 10 software. Three key themes emerged from qualitative analysis: Most participants reported (a) financial barriers, (b) fluctuations in insurance status and challenges with insurance re-enrollment, and (c) lack of access to a provider and discomfort discussing sexual health as barriers to accessing HIV/sexually transmitted disease care in primary care settings. Hispanic/Latino men more frequently cited these barriers compared with non-Hispanic White men. Insurance status and out-of-pocket costs are barriers to sexual health care for at-risk men.
Hearing Preservation in Cochlear Implant Surgery: A Meta-Analysis
Authors: Snels Chantal , IntHout Joanna , Mylanus Emmanuel , Huinck Wendy , Dhooge Ingeborg
Published: January 2019

Objective(s):

The aim of the present meta-analysis is to assess the effects of hearing preservation (HP) methods on residual hearing in patients undergoing cochlear implant (CI) surgery and to look at the effect of follow-up time on HP outcome.

Data Sources:

A systematic search was conducted in PubMed, Embase, and Cochrane Library. Only articles in English were included.

Study Selection:

Prospective studies published until January 2018 on hearing preservation methods were included.

Data Extraction:

Studies were assessed on unaided pre- and postoperative hearing thresholds, follow up time, and methodological quality.

Data Synthesis:

A random-effects meta-regression was performed for the HP outcome in relation to surgical technique, electrode array design, inserted electrode length, insertion speed, and corticosteroid use for different follow up times (1 month, 6 months, and 12 months or more postoperatively).

Conclusion:

Hearing preservation in cochlear implant surgery is feasible. A statistically significant difference was found between the round window procedure and cochleostomy approach, in favor of the round window procedure at 6 months postoperatively (p = 0.001). A statistically significant difference was found between the straight and the perimodiolar electrode array at 1 month postoperatively in favor of the straight electrode array (p < 0.001). No statistically significant difference was found between the other HP methods. The round window approach with the straight electrode array might result in a better HP outcome at 1 month and 6 months postoperatively compared with the cochleostomy approach with the perimodiolar electrode array. A declining trend in HP outcome in both combinations was seen over time.
Factors Influencing Access to Cochlear Implantation in Deaf and Hard-of-Hearing Children in Southern California
Authors: Moshtaghi Omid , Kuan Edward C. , Mahboubi Hossein , Khoshab Nima , Zardouz Shawn , Yau Amy Yuk-Yee , Rothholtz Vanessa S. , Lin Harrison W. , Djalilian Hamid R.
Published: January 2019

Objective:

To determine the epidemiologic relationship of family demographics and educational resources with parental knowledge of and willingness for their children to receive cochlear implantation (CI) for deaf and hard-of-hearing (DHH) children.

Methods:

A total of 213 parents of DHH children were surveyed at local schools, specialized camps, and clinics in Southern California. Data on parents were solicited, including income, insurance status, education level, hearing status, primary language, and motivations towards CI.

Results:

Sixty-six surveys were included in the analysis. Three of these patients had already undergone CI, thus of the 63 children without CI, 59% had been presented with the option of CI by a healthcare professional and 27% were willing to have their child undergo CI. Willingness for children to undergo CI was statistically higher in families with an annual income less than $15,000 or more than $75,000 (p = 0.02), and children enrolled in specialized schools for DHH (p = 0.02). The leading reasons for unwillingness to undergo CI were risks of surgery (17%) and discouragement from others (14%).

Conclusion:

A significant gap exists between the number of CI candidates and families and willingness to undergo CI. The difference could be related to socioeconomic status and the patient's school type. This underscores the importance of parental education through the use of a multi-disciplinary team to ensure all hearing rehabilitation options are explained.