Infrared imaging enhances retinal crystals in Bietti's crystalline dystrophy.

PubMed

Brar, Vikram S; Benson, William H

2015-01-01

Infrared imaging dramatically increased the number of crystalline deposits visualized compared with clinical examination, standard color fundus photography, and red free imaging in patients with Bietti's crystalline dystrophy. We believe that this imaging modality significantly improves the sensitivity with which these lesions are detected, facilitating earlier diagnosis and may potentially serve as a prognostic indicator when examined over time.

Creating a high-value delivery system for health care.

PubMed

Teisberg, Elizabeth O; Wallace, Scott

2009-01-01

Health care reform that focuses on improving value enhances both the well-being of patients and the professional satisfaction of physicians. Value in health care is the improvement in health outcomes achieved for patients relative to the money spent. Dramatic and ongoing improvement in the value of health care delivered will require fundamental restructuring of the system. Current efforts to improve safety and reduce waste are truly important but not sufficient. The following three structural changes will drive simultaneous improvement in outcomes and efficiency: (1) reorganizing care delivery into clinically integrated teams defined by patient needs over the full cycle of care; (2) measuring and reporting patient outcomes by clinical teams, across the cycle of care and for identified clusters of medical circumstances; and (3) enabling reimbursement tied to value rather than to quantity of services. Many of these changes require physician leadership. We discuss steps on the journey to value-based care delivery.

Improving efficiency and access to mental health care: combining integrated care and advanced access.

PubMed

Pomerantz, Andrew; Cole, Brady H; Watts, Bradley V; Weeks, William B

2008-01-01

To provide an example of implementation of a new program that enhances access to mental health care in primary care. A general and specialized mental health service was redesigned to introduce open access to comprehensive mental health care in a primary care clinic. Key variables measured before and after implementation of the clinic included numbers of completed referrals, waiting time for appointments and clinic productivity. Workload and pre/post-implementation waiting time data were gathered through a computerized electronic monitoring system. Waiting time for new appointments was shortened from a mean of 33 days to 19 min. Clinician productivity and evaluations of new referrals more than doubled. These improvements have been sustained for 4 years. Moving mental health services into primary care, initiating open access and increasing use of technological aids led to dramatic improvements in access to mental health care and efficient use of resources. Implementation and sustainability of the program were enhanced by using a quality improvement approach.

The Burn Wound Microenvironment

PubMed Central

Rose, Lloyd F.; Chan, Rodney K.

2016-01-01

Significance: While the survival rate of the severely burned patient has improved significantly, relatively little progress has been made in treatment or prevention of burn-induced long-term sequelae, such as contraction and fibrosis. Recent Advances: Our knowledge of the molecular pathways involved in burn wounds has increased dramatically, and technological advances now allow large-scale genomic studies, providing a global view of wound healing processes. Critical Issues: Translating findings from a large number of in vitro and preclinical animal studies into clinical practice represents a gap in our understanding, and the failures of a number of clinical trials suggest that targeting single pathways or cytokines may not be the best approach. Significant opportunities for improvement exist. Future Directions: Study of the underlying molecular influences of burn wound healing progression will undoubtedly continue as an active research focus. Increasing our knowledge of these processes will identify additional therapeutic targets, supporting informed clinical studies that translate into clinical relevance and practice. PMID:26989577

Infrared imaging enhances retinal crystals in Bietti’s crystalline dystrophy

PubMed Central

Brar, Vikram S; Benson, William H

2015-01-01

Infrared imaging dramatically increased the number of crystalline deposits visualized compared with clinical examination, standard color fundus photography, and red free imaging in patients with Bietti’s crystalline dystrophy. We believe that this imaging modality significantly improves the sensitivity with which these lesions are detected, facilitating earlier diagnosis and may potentially serve as a prognostic indicator when examined over time. PMID:25931805

A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial.

PubMed

Dainty, Katie N; Scales, Damon C; Brooks, Steve C; Needham, Dale M; Dorian, Paul; Ferguson, Niall; Rubenfeld, Gordon; Wax, Randy; Zwarenstein, Merrick; Thorpe, Kevin; Morrison, Laurie J

2011-01-14

Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay. This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes. Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner. ClinicalTrials.gov Trial Identifier: NCT00683683.

Development trends for new cancer therapeutics and vaccines.

PubMed

Reichert, Janice M; Wenger, Julia B

2008-01-01

Global commercial development of cancer treatments has dramatically increased over the past 15 years. To assess trends in the process, we analyzed data for 1111 candidates that entered clinical study during 1990-2006. Our results show that although the average number of therapeutic candidates entering clinical study per year more than doubled, the US approval success rate was low (8%) during the period. The therapeutics took seven years on average to go through the clinical and US approval phases, but cancer vaccines have yet to gain any US approvals. These results indicate that improvement in the efficiency of the development process for innovative cancer treatments is needed.

The Safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs

PubMed Central

Kim, Joon-young; Han, Hyun-jung; Yun, Hun-young; Lee, Bora; Jang, Ha-young; Eom, Ki-dong; Park, Hee-myung

2008-01-01

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month follow-up, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse. PMID:18296893

Impact of voice- and knowledge-enabled clinical reporting--US example.

PubMed

Bushko, Renata G; Havlicek, Penny L; Deppert, Edward; Epner, Stephen

2002-01-01

This study shows qualitative and quantitative estimates of the national and the clinic level impact of utilizing voice and knowledge enabled clinical reporting systems. Using common sense estimation methodology, we show that the delivery of health care can experience a dramatic improvement in four areas as a result of the broad use of voice and knowledge enabled clinical reporting: (1) Process Quality as measured by cost savings, (2) Organizational Quality as measured by compliance, (3) Clinical Quality as measured by clinical outcomes and (4) Service Quality as measured by patient satisfaction. If only 15 percent of US physicians replaced transcription with modem clinical reporting voice-based methodology, about one half billion dollars could be saved. $6.7 Billion could be saved annually if all medical reporting currently transcribed was handled with voice-and knowledge-enabled dictation and reporting systems.

Technology for Improving Medication Monitoring in Nursing Homes

DTIC Science & Technology

2005-01-01

been a dramatic change in the distribution of age in the general population, with elderly persons, particularly those over the age of 80 years... health care professionals with expertise in geriatric pharmacotherapy. The goal of the GRAM software is to assist in the implementation of the...in mind, this clinical tool may be used by pharmacists or other health professionals in all settings of geriatric care. Identify/Collect

The role of ablative lasers in cutaneous scars: tissue regeneration to restore function (Conference Presentation)

NASA Astrophysics Data System (ADS)

Uebelhoer, Nathan

2017-02-01

Many laser wavelengths with various power and pulse characteristics have been used in an attempt to improve cutaneous scars. No single configuration has produced such dramatic changes in quality of life as the high energy, low density, sub-millisecond pulsed ablative infrared laser. Hundreds of wounded military service members with burn and traumatic scars that resulted in disabling restriction in range of motion have been treated since 2008. By fractionating the pulse to produce a uniform thermal injury less than 400um wide and to a depth of 3mm into the scar, we have observed dramatic reductions in scar-induced pain, pruritus, and most significantly, improvements in range of motion. The clinical and histologic changes seen in restrictive scars following treatment correlates with a regeneration of tissue that appears and functions more like normal tissue rather than scar. This lecture will describe our experience in the military and the latest research to support our observations.

Action, Not Rhetoric, Needed to Reverse the Opioid Overdose Epidemic.

PubMed

Davis, Corey; Green, Traci; Beletsky, Leo

2017-03-01

Despite shifts in rhetoric and some positive movement, Americans with the disease of addiction are still often stigmatized, criminalized, and denied access to evidencebased care. Dramatically reducing the number of lives unnecessarily lost to overdose requires an evidence-based, equity-focused, well-funded, and coordinated response. We present in this brief article evidence-based and promising practices for improving and refocusing the response to this simmering public health crisis. Topics covered include improving clinical decision-making, improving access to non-judgmental evidence-based treatment, investing in comprehensive public health approaches to problematic drug use, and changing the way law enforcement actors interact with people who use drugs.

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.

PubMed

Kleikers, Pamela W M; Hooijmans, Carlijn; Göb, Eva; Langhauser, Friederike; Rewell, Sarah S J; Radermacher, Kim; Ritskes-Hoitinga, Merel; Howells, David W; Kleinschnitz, Christoph; Schmidt, Harald H H W

2015-08-27

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.

Boxing-related head injuries.

PubMed

Jayarao, Mayur; Chin, Lawrence S; Cantu, Robert C

2010-10-01

Fatalities in boxing are most often due to traumatic brain injury that occurs in the ring. In the past 30 years, significant improvements in ringside and medical equipment, safety, and regulations have resulted in a dramatic reduction in the fatality rate. Nonetheless, the rate of boxing-related head injuries, particularly concussions, remains unknown, due in large part to its variability in clinical presentation. Furthermore, the significance of repeat concussions sustained when boxing is just now being understood. In this article, we identify the clinical manifestations, pathophysiology, and management of boxing-related head injuries, and discuss preventive strategies to reduce head injuries sustained by boxers.

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

PubMed

Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

A Domain Analysis Model for eIRB Systems: Addressing the Weak Link in Clinical Research Informatics

PubMed Central

He, Shan; Narus, Scott P.; Facelli, Julio C.; Lau, Lee Min; Botkin, Jefferey R.; Hurdle, John F.

2014-01-01

Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. PMID:24929181

Effects and safety of 99Tc-MDP in patients with refractory ankylosing spondylitis: a 2-stage (30-week follow-up) clinical trial.

PubMed

Xu, Yunyun; Zhong, Yi; Zhao, Minjing; Tu, Liudan; Fan, Meida; Zhang, Pingping; Wei, Qiujing; Cao, Shuangyan; Li, Qiuxia; Liao, Zetao; Lin, Zhiming; Pan, Yunfeng; Jin, Ou; Gu, Jieruo

2018-01-01

To evaluate the clinical efficacy and safety in patients with refractory ankylosing spondylitis (AS) initiating 99Tc-MDP therapy and explore the mechanisms. Refractory AS patients were enrolled in the clinical trial and received 99Tc-MDP treatments for 3 or 5 courses according to ASAS improvement. Efficacy and safety evaluations were conducted during the follow-up. 37 cytokines were quantified by Luminex at baseline and week 30. p-values<0.05 were considered statistically significant. 51 refractory AS patients were included, with 20 healthy people serving as the control group. The patients were in an active disease state (mean (SD) ASDAS 3.66 (0.83), BASDAI 4.53 (1.92)), 42(82.35%) patients had syndesmophytes. Their cytokines were significantly higher than that in the control group. After 3 courses of 99Tc-MDP treatment, 32 (62.75%) patients achieved ASAS20 improvement, 24 (47.06%) patients achieved a clinically significant improvement (ΔASDAS-CRP≥1.1). 27 patients entered the second stage to complete 5 courses of the treatment, all of whom achieved ASAS20 improvement, 18 (66.67%) patients achieved a clinically significant improvement. All clinical parameters including ASAS and ASDAS significantly improved as the treatment was continued. Cytokines also had significant down-regulation after the treatment, and the reductions had positive correlations with the improvements of disease activity. No serious adverse event was observed. This investigation confirmed the remarkable efficacy of 99Tc-MDP in a large number of refractory AS patients, and highlighted the mechanism by dramatic regulation on cytokines. 99Tc-MDP was safe in clinical application.

The osteogenic capacity of biomimetic hierarchical micropore/nanorod-patterned Sr-HA coatings with different interrod spacings.

PubMed

Zhou, Jianhong; Li, Bo; Han, Yong; Zhao, Lingzhou

2016-07-01

Advanced titanium based bone implant with fast established, rigid and stable osseointegration is stringently needed in clinic. Here the hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca9Sr1(PO4)6(OH)2, Sr1-HA) coatings (MNRs) with different interrod spacings varying from about 300 to 33nm were developed. MNRs showed dramatically differential biological performance closely related to the interrod spacing. Compared to micropore/nanogranule-patterned Sr1-HA coating (MNG), MNRs with an interrod spacing of larger than 137nm resulted in inhibited in vitro mesenchymal stem cell functions and in vivo osseointegration, while those of smaller than 96nm gave rise to dramatically enhanced the biological effect, especially those of mean 67nm displayed the best effect. The differential biological effect of MNRs was related to their modulation on the focal adhesion mediated mechanotransduction. These results suggest that MNRs with a mean interrod spacing of 67nm may give rise to an advanced implant of improved clinical performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Dramatic response to alectinib in a patient of ALK-rearranged lung cancer with poor performance status.

PubMed

Tanaka, Hisashi; Taima, Kageaki; Morimoto, Takeshi; Nakamura, Kunihiko; Tanaka, Yoshihito; Itoga, Masamichi; Takanashi, Shingo; Okumura, Ken

2016-03-17

Lung cancers with anaplastic lymphoma kinase rearrangements are highly sensitive to anaplastic lymphoma kinase tyrosine kinase inhibition, underscoring the notion that such cancers are addicted to anaplastic lymphoma kinase activity. Several anaplastic lymphoma kinase inhibitors have been identified and are being evaluated in clinical trials. However patients with poor performance status (3 or 4) were not involved in these clinical trials, it has been unclear to use anaplastic lymphoma kinase-tyrosine kinase inhibitors for these patients. Here, we report an anaplastic lymphoma kinase-positive non small cell lung cancer patient with performance status 4, who was successfully treated with alectinib. We report on a 52-year-old patient diagnosed as non small cell lung cancer harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene. His performance status was 4 because of severe respiratory failure. We treated this patient with alectinib as the first line therapy. Dramatic response was obtained and his performance status improved from 4 to 1 without severe adverse events. Alectinib is a therapeutic option for the anaplastic lymphoma kinase positive patients with poor performance status.

Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions

PubMed Central

Neufeld, Ellis J.

2006-01-01

For nearly 30 years, patients with transfusional iron overload have depended on nightly deferoxamine infusions for iron chelation. Despite dramatic gains in life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, the leading cause of death for young adults with thalassemia major and related disorders has been cardiac disease from myocardial iron deposition. Strategies to reduce cardiac disease by improving chelation regimens have been of the highest priority. These strategies have included development of novel oral iron chelators to improve compliance, improved assessment of cardiac iron status, and careful epidemiologic assessment of European outcomes with deferiprone, an oral alternative chelator available for about a decade. Each of these strategies is now bearing fruit. The novel oral chelator deferasirox was recently approved by the Food and Drug Administration (FDA); a randomized clinical trial demonstrates that deferasirox at 20 to 30 mg/kg/d can maintain or improve hepatic iron in thalassemia as well as deferoxamine. A randomized trial based on cardiac T2* magnetic resonance imaging (MRI) suggests that deferiprone can unload myocardial iron faster than deferoxamine. Retrospective epidemiologic data suggest dramatic reductions in cardiac events and mortality in Italian subjects exposed to deferiprone compared with deferoxamine. These developments herald a new era for iron chelation, but many unanswered questions remain. PMID:16627763

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct.

PubMed

Lee, Howard; Lee, Heechan; Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. A total of 114 failure modes were identified with an RPN score ranging 3-378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes.

Acute visceral cysticercosis by Taenia hydatigena in lambs and treatment with praziquantel.

PubMed

Scala, A; Urrai, G; Varcasia, A; Nicolussi, P; Mulas, M; Goddi, L; Pipia, A P; Sanna, G; Genchi, M; Bandino, E

2016-01-01

An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of 21 (23.8%) female lambs, is reported. Gross post-mortem examinations and histology showed Cysticercus tenuicollis as the cause of death. Biochemical parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the clinical condition and biochemical parameters was observed up to 30 days following treatment.

Vulval lichen planus-lichen sclerosus overlap.

PubMed

Howard, Matthew; Hall, Anthony

2018-01-01

Vulval lichen planus-lichen sclerosus overlap is an emerging observation. Few clinical reports exist with no reviews of literature. We present a focused update of this phenomenon and discuss a clinical case. We report a 63-year-old woman with a 20-year history of ulcerative vulvo-vaginitis, initially diagnosed as benign mucous membrane (cicatricial) pemphigoid. This led to prolonged treatment with oral corticosteroids with minimal improvement in symptoms. Subsequent complications of long-term use of systemic corticosteroid ensued. A clinico-pathological diagnosis of severe erosive lichen planus was made on clinical findings and on non-specific biopsy changes of ulceration and inflammation. Treatment with topical clobetasol propionate 0.05% ointment twice daily led to dramatic improvement of ulceration, easing of discomfort and marked improvement in quality of life. Clinical examination revealed Wickham's striae on the labia majora supporting the diagnosis. Six years after commencement of topical clobetasol, white plaques were noticed on the labia majora, perineum and peri-anal region consistent with lichen sclerosus, confirmed by repeat vulval skin biopsy and on vulvectomy. This case highlights the challenge of diagnosis of extensive vulvo-vaginal ulceration and the necessity to re-examine a previous diagnosis if there is poor response to treatment.

Nitrous Oxide Abuse and Vitamin B12 Action in a 20-Year-Old Woman: A Case Report.

PubMed

Duque, Miriam Andrea; Kresak, Jesse L; Falchook, Adam; Harris, Neil S

2015-01-01

Herein, we report a case of a 20-year-old (ethnicity not reported) woman with a history of nitrous oxide abuse and clinical symptoms consistent with spinal cord subacute combined degeneration with associated low serum concentrations of vitamin B12, elevated methylmalonic acid levels, and radiologic evidence of demyelination of the dorsal region of the spinal column. The health of the patient improved dramatically with B12 supplementation. In this case, we discuss the interaction of nitrous oxide with the enzymatic pathways involved in the biochemistry of vitamin B12. Copyright© by the American Society for Clinical Pathology (ASCP).

Oncogenic drivers, targeted therapies, and acquired resistance in non-small-cell lung cancer.

PubMed

Gower, Arjan; Wang, Yisong; Giaccone, Giuseppe

2014-07-01

In the past decade, a shift toward targeted therapies in non-small-cell lung cancer following molecular profiling has dramatically changed the way advanced adenocarcinoma is treated. However, tumor cells inevitably acquire resistance to such therapies, circumventing any sustained clinical benefit. As the genomic classification of lung cancer continues to evolve and as the mechanisms of acquired resistance to targeted therapies become elucidated and more improved target-specific drugs come into sight, the future will see more promising results from the clinic through the development of new therapeutic strategies to overcome, or prevent the development of, resistance for lung cancer patients.

Brachial Plexus Injuries in Adults: Evaluation and Diagnostic Approach

PubMed Central

Sakellariou, Vasileios I.; Badilas, Nikolaos K.; Mazis, George A.; Stavropoulos, Nikolaos A.; Kotoulas, Helias K.; Kyriakopoulos, Stamatios; Tagkalegkas, Ioannis; Sofianos, Ioannis P.

2014-01-01

The increased incidence of motor vehicle accidents during the past century has been associated with a significant increase in brachial plexus injuries. New imaging studies are currently available for the evaluation of brachial plexus injuries. Myelography, CT myelography, and magnetic resonance imaging (MRI) are indicated in the evaluation of brachial plexus. Moreover, a series of specialized electrodiagnostic and nerve conduction studies in association with the clinical findings during the neurologic examination can provide information regarding the location of the lesion, the severity of trauma, and expected clinical outcome. Improvements in diagnostic approaches and microsurgical techniques have dramatically changed the prognosis and functional outcome of these types of injuries. PMID:24967130

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.

PubMed

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-11-05

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.

Combination Controversies: Checkpoint Inhibition Alone or in Combination for the Treatment of Melanoma?

PubMed

Warner, Allison Betof; Postow, Michael A

2018-05-15

The immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have dramatically improved outcomes for patients with metastatic melanoma; however, not all patients benefit from monotherapy with these agents. To address this issue, complementary combinations of immunotherapy are increasingly being explored as a strategy to improve outcomes. However, combinatorial approaches come with heightened risk of toxicity. In this review, we highlight combinations for which there are prospective data from clinical trials. The combinations discussed include ipilimumab plus anti-programmed death 1 agents, ipilimumab plus granulocyte-macrophage colony-stimulating factor, checkpoint inhibitor plus talimogene laherparepvec, ipilimumab plus chemotherapy, checkpoint inhibitor plus BRAF/MEK targeted therapy, and checkpoint inhibition plus radiation therapy. We discuss data regarding the efficacy and toxicity of combination therapy, and we identify clinical scenarios that may favor treatment with combination therapy.

Simplifying study of fever's dramatic relief of autistic behavior.

PubMed

Good, Peter

2017-02-01

Dramatic relief of autistic behavior by infectious fever continues to tantalize parents and practitioners, yet researchers still hesitate to study its physiology/biochemistry, fearing stress and heat of brain imaging, contagion, and fever's complexity. Yet what could be more revealing than a common event that virtually 'normalizes' autistic behavior for a time? This paper proposes study of three simplified scenarios: (1) improvements appearing hours before fever, (2) return of autistic behavior soon after fever, (3) improvements persisting long after fever. Each scenario limits some risk - and some explanation - inviting triangulation of decisive factor(s) in relief and recurrence. Return of autistic behavior after fever may be most revealing. The complex mechanisms that generated fever have all abated; simpler cooling mechanisms prevail - how many plausible explanations can there be? The decisive factor in fever's benefit is concluded to be water drawn/carried from brain myelin and astrocytes by osmolytes glutamine and taurine released from muscles and brain; the decisive factor in return of autistic behavior after fever is return of water. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Achilles tendinopathy: A prospective study on the effect of active rehabilitation and steroid injections in a clinical setting.

PubMed

Wetke, E; Johannsen, F; Langberg, H

2015-08-01

In published efficacy studies on Achilles tendinopathy (AT) exercise alone results in improvement in 60-90% of the cases. However, this high success rate cannot be expected in usual clinical practice. We prospectively investigated the effectiveness of a treatment regimen consisting of home-based exercises (concentric, eccentric, and stretching) and optional glucocorticosteroid (GCS) injections in patients with (AT) in a usual clinical setting. Patients unable to commence or progress in exercise were offered GCS, hypothesizing that the GCS would facilitate exercise. Ninety-three consecutive patients with AT referred to two outpatient rheumatology clinics were registered, and seen at five visits over a 6-month period. Exercises seemed to have a slow, but long-lasting effect with GCS having a dramatic short-term effect on symptoms. Twenty-six percent of the patients could proceed with training alone, the remainder received one to three supplementary GCS. There were significant improvements on all outcome variables over time (P ≤ 0.001). At follow-up, 42 had no more symptoms, 29 good result, 16 slightly improved, 4 unchanged, and 2 slightly worse. Overall, 94% of the patients had improved, and we thus recommend the use of GCS injections in AT patients if training alone does not lead to improvement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Video Taping and Abnormal Psychology: Dramatized Clinical Interviews.

ERIC Educational Resources Information Center

Lyons, Michael J.; And Others

1984-01-01

Students in an abnormal psychology course worked in teams to produce dramatizations of diagnostic interviews and then presented them in class. Positive and negative aspects of the activity are discussed. (RM)

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

PubMed Central

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-01-01

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation. PMID:18986533

Dramatic pretend play games uniquely improve emotional control in young children.

PubMed

Goldstein, Thalia R; Lerner, Matthew D

2017-09-15

Pretense is a naturally occurring, apparently universal activity for typically developing children. Yet its function and effects remain unclear. One theorized possibility is that pretense activities, such as dramatic pretend play games, are a possible causal path to improve children's emotional development. Social and emotional skills, particularly emotional control, are critically important for social development, as well as academic performance and later life success. However, the study of such approaches has been criticized for potential bias and lack of rigor, precluding the ability to make strong causal claims. We conducted a randomized, component control (dismantling) trial of dramatic pretend play games with a low-SES group of 4-year-old children (N = 97) to test whether such practice yields generalized improvements in multiple social and emotional outcomes. We found specific effects of dramatic play games only on emotional self-control. Results suggest that dramatic pretend play games involving physicalizing emotional states and traits, pretending to be animals and human characters, and engaging in pretend scenarios in a small group may improve children's emotional control. These findings have implications for the function of pretense and design of interventions to improve emotional control in typical and atypical populations. Further, they provide support for the unique role of dramatic pretend play games for young children, particularly those from low-income backgrounds. A video abstract of this article can be viewed at: https://youtu.be/2GVNcWKRHPk. © 2017 John Wiley & Sons Ltd.

Driving out errors through tight integration between software and automation.

PubMed

Reifsteck, Mark; Swanson, Thomas; Dallas, Mary

2006-01-01

A clear case has been made for using clinical IT to improve medication safety, particularly bar-code point-of-care medication administration and computerized practitioner order entry (CPOE) with clinical decision support. The equally important role of automation has been overlooked. When the two are tightly integrated, with pharmacy information serving as a hub, the distinctions between software and automation become blurred. A true end-to-end medication management system drives out errors from the dockside to the bedside. Presbyterian Healthcare Services in Albuquerque has been building such a system since 1999, beginning by automating pharmacy operations to support bar-coded medication administration. Encouraged by those results, it then began layering on software to further support clinician workflow and improve communication, culminating with the deployment of CPOE and clinical decision support. This combination, plus a hard-wired culture of safety, has resulted in a dramatically lower mortality and harm rate that could not have been achieved with a partial solution.

Systemic antimicrobial therapy (minocycline) as an adjunct to non-surgical approach to recurrent chronic generalized gingival hyperplasia.

PubMed

Khatri, Parag M; Bacha, Shraddanand

2014-03-01

Systemic antibiotic treatment has emerged as a powerful adjunct to conventional mechanical debridement for therapeutic management of the periodontal diseases. The conceptual basis for treating periodontal diseases as infections is particularly attractive in part because of substantial data indicating that these diseases may be associated with specific putative pathogens. Further, discrete groups of patients respond well to systemic antibiotics and exhibit improvement of clinical parameters, including attachment level and inflammation. This bacterial-host interaction, which is ever-so-present in periodontitis, directs us toward utilizing antimicrobial agents along with the routine mechanical debridement. This case report presents a case of a female patient with recurrence of the chronic generalized periodontitis with gingival enlargement, which is treated thrice by referral dentist. A through clinical examination was carried out pre-operatively and treatment was planned with systemic minocycline in conjunction with the conventional non-surgical approach. There was a significant reduction of pocket depth, gain in attachment with dramatic improvement clinically.

[Rapid resolution of acute subdural haematoma with significant impact on clinical outcome].

PubMed

Capion, Tenna; Lilja-Cyron, Alexander; Kelsen, Jesper

2017-09-04

A 73-year-old woman was admitted to hospital due to anaemia. She suffered a minor head trauma and deteriorated to deep unconsciousness. A CT revealed an acute subdural haematoma (ASDH). Initially, she was not found to be a candidate for neurosurgical intervention, but within 24 hours her level of consciousness improved dramatically, and a renewed CT showed resolution of the ASDH. She underwent acute craniotomy with good outcome. This illustrates the importance of re-evaluation of patients with intracranial haemorrhage.

Sarcoid granuloma of the choroid.

PubMed

Marcus, D F; Bovino, J A; Burton, T C

1982-12-01

Two patients were found to have macular choroidal granulomas associated with systemic sarcoidosis. This unusual fundus picture was documented by serial fundus photography and fluorescein angiography. Both patients had a similar clinical picture of decreased vision, chorioretinal granulomas, and overlying neurosensory detachments. Staining of the inflammatory mass with fluorescein and leakage of dye into the neurosensory space was typical. Lymph node biopsies were performed to substantiate the diagnosis. Both patients responded promptly to systemic corticosteroid therapy with dramatic improvement in visual acuity and resolution of the choroidal lesions.

Giving them a good start: informatics support of newborn screening and clinical care.

PubMed

Wetter, T; Haschler, I; Ho, S; Hoffmann, G F; Linderkamp, O; Philipp, F; Skonetzki, S

2005-01-01

Newborns are a vulnerable population: Exposed to dramatically changing environmental conditions, potentially suffering from impairments that cannot realistically be diagnosed during pregnancy, with the risk that unfavorable conditions escalate fast. We have investigated informatics methods and tools to make screening for congenital diseases and containment of critical processes that start in the first days safer and more efficient. This poster present a set of three different methodological approaches that all aim at comprehensive improvement of neonatal care.

Diabetes mellitus disease management in a safety net hospital system: translating evidence into practice.

PubMed

Butler, Michael K; Kaiser, Michael; Johnson, Jolene; Besse, Jay; Horswell, Ronald

2010-12-01

The Louisiana State University Health Care Services Division system assessed the effectiveness of implementing a multisite disease management program targeting diabetes mellitus in an indigent patient population. A population-based disease management program centered on evidence-based clinical care guidelines was applied from the system level. Specific clinic modifications and models were used, as well as ancillary services such as medication assistance and equipment subsidies. Marked improvement in process goals led to improved clinical outcomes. From 2001 to 2008, the percentage of patients with a hemoglobin A1c < 7.0 increased from 45% to 55% on the system level, with some sites experiencing a more dramatic shift. Results were similar across sites, which included both small provider groups and academic health centers. In order to achieve these results, the clinical environment changed to promote those evidence-based interventions. Even in complex environments such as academic health centers with several provider levels, or those environments with limited care resources, disease management programs can be successfully implemented and achieve statistically significant results.

A patient with Cotard syndrome who showed an improvement in single photon emission computed tomography findings after successful treatment with antidepressants.

PubMed

Hashioka, Sadayuki; Monji, Akira; Sasaki, Masayuki; Yoshida, Ichiro; Baba, Kanji; Tashiro, Nobutada

2002-01-01

We report the case of a presenile woman with Cotard syndrome, in the context of major depression, who showed an improvement in bilateral frontal hypoperfusion in a SPECT study using 99mTc-HMPAO after undergoing successful treatment with antidepressant therapy. We also retrospectively evaluated her clinical course based on the clinical stages. The symptoms of Cotard syndrome have been reported to change dramatically according to the stages. This peculiarity made it difficult for us to rapidly diagnose Cotard syndrome in the context of major depression, and not dementia, and thereby adequately treat the patient in our case. Differences in the reduced blood flow regions and a time lag from psychiatric remission were observed before the improvement in the SPECT findings when comparing our case with a previously reported case of Cotard syndrome. These differences suggest that the mechanism of Cotard syndrome is still not well understood at the present time.

Multiscale modelling and nonlinear simulation of vascular tumour growth

PubMed Central

Macklin, Paul; Anderson, Alexander R. A.; Chaplain, Mark A. J.; Cristini, Vittorio

2011-01-01

In this article, we present a new multiscale mathematical model for solid tumour growth which couples an improved model of tumour invasion with a model of tumour-induced angiogenesis. We perform nonlinear simulations of the multi-scale model that demonstrate the importance of the coupling between the development and remodeling of the vascular network, the blood flow through the network and the tumour progression. Consistent with clinical observations, the hydrostatic stress generated by tumour cell proliferation shuts down large portions of the vascular network dramatically affecting the flow, the subsequent network remodeling, the delivery of nutrients to the tumour and the subsequent tumour progression. In addition, extracellular matrix degradation by tumour cells is seen to have a dramatic affect on both the development of the vascular network and the growth response of the tumour. In particular, the newly developing vessels tend to encapsulate, rather than penetrate, the tumour and are thus less effective in delivering nutrients. PMID:18781303

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct

PubMed Central

Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Background Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. Methods A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. Results A total of 114 failure modes were identified with an RPN score ranging 3–378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. Conclusions FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes. PMID:29089745

Regenerative Endodontics: A Road Less Travelled

PubMed Central

Bansal, Ramta; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

2014-01-01

Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering. PMID:25478476

The role of lasers and intense pulsed light technology in dermatology

PubMed Central

Husain, Zain; Alster, Tina S

2016-01-01

The role of light-based technologies in dermatology has expanded dramatically in recent years. Lasers and intense pulsed light have been used to safely and effectively treat a diverse array of cutaneous conditions, including vascular and pigmented lesions, tattoos, scars, and undesired hair, while also providing extensive therapeutic options for cosmetic rejuvenation and other dermatologic conditions. Dermatologic laser procedures are becoming increasingly popular worldwide, and demand for them has fueled new innovations and clinical applications. These systems continue to evolve and provide enhanced therapeutic outcomes with improved safety profiles. This review highlights the important roles and varied clinical applications that lasers and intense pulsed light play in the dermatologic practice. PMID:26893574

Clinical and Community Strategies to Prevent Falls and Fall-Related Injuries Among Community-Dwelling Older Adults.

PubMed

Taylor-Piliae, Ruth E; Peterson, Rachel; Mohler, Martha Jane

2017-09-01

Falls in older adults are the result of several risk factors across biological and behavioral aspects of the person, along with environmental factors. Falls can trigger a downward spiral in activities of daily living, independence, and overall health outcomes. Clinicians who care for older adults should screen them annually for falls. A multifactorial comprehensive clinical fall assessment coupled with tailored interventions can result in a dramatic public health impact, while improving older adult quality of life. For community-dwelling older adults, effective fall prevention has the potential to reduce serious fall-related injuries, emergency room visits, hospitalizations, institutionalization, and functional decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis.

PubMed

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N K

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians.

Assessment of patients for treatment with tinnitus retraining therapy.

PubMed

Henry, James A; Jastreboff, Margaret M; Jastreboff, Pawel J; Schechter, Martin A; Fausti, Stephen A

2002-01-01

Clinical management for patients complaining of severe tinnitus has improved dramatically in the last 25 years. During that period of time, various methods of treatment have been introduced and are being used with varying degrees of success. One method that has received considerable attention is tinnitus retraining therapy (TRT). This method is being practiced by hundreds of clinicians worldwide, and retrospective clinical data indicate that TRT has been effective for the majority of patients. This article provides a guide for clinicians to evaluate their patients for treatment with TRT. Included in this guide is the expanded version of the TRT initial interview and specific instructions for the clinician administering the interview.

Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma.

PubMed

Nakanishi, Yosuke; Wakisaka, Naohiro; Kondo, Satoru; Endo, Kazuhira; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Yoshizaki, Tomokazu

2017-09-01

Nasopharyngeal carcinoma (NPC) is very common in southern China and Southeast Asia. In regions where NPC is endemic, undifferentiated subtypes constitute most cases and are invariably associated with Epstein-Barr virus (EBV) infection, whereas the differentiated subtype is more common in other parts of the world. Undifferentiated NPC is a unique malignancy with regard to its epidemiology, etiology, and clinical presentation. Clinically, NPC is highly invasive and metastatic, but sensitive to both chemotherapy and radiotherapy (RT). Overall prognosis has dramatically improved over the past three decades because of advances in management, including the improvement of RT technology, the broader application of chemotherapy, and more accurate disease staging. Despite the excellent local control with modern RT, distant failure remains a challenging problem. Advances in molecular technology have helped to elucidate the molecular pathogenesis of NPC. This article reviews the contribution of EBV gene products to NPC pathogenesis and the current management of NPC.

Type I Chiari malformation presenting central sleep apnea.

PubMed

Kitamura, Takuro; Miyazaki, Soichiro; Kadotani, Hiroshi; Kanemura, Takashi; Okawa, Masako; Tanaka, Toshihiko; Komada, Ichiro; Hatano, Taketo; Suzuki, Hideaki

2014-04-01

Sleep apnea is a rare but a well-known clinical feature of type I Chiari malformation. It may be obstructive or central in nature. Sleep apnea in patients with type I Chiari malformation rarely presents without accompanying neurological signs or symptoms. We here report a case of a 10-year-old girl who presented with central sleep apnea without any other neurological signs but was ultimately diagnosed with type I Chiari malformation. The patient initially showed mild improvement in symptoms after administration of an acetazolamide. Finally, posterior fossa decompression dramatically improved her respiratory status during sleep, both clinically and on polysomnography. This case suggests that type I Chiari malformation should be considered in the differential diagnoses of central apneas in children, even if there are no other neurological signs and symptoms. Furthermore, sagittal craniocervical magnetic resonance imaging may be necessary for a definitive diagnosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[The transsexualism syndrome: clinical aspects and therapeutic prospects].

PubMed

Gallarda, T; Amado, I; Coussinoux, S; Poirier, M F; Cordier, B; Olié, J P

1997-01-01

The prevalence rate of transsexualism varies from 1 to 50,000, to 1 to 100,000. Although it remains an infrequent affliction, transsexualism generates usually major suffering and may be responsible of many complications like suicide, self-mutilations, affective disorders and social disabilities. Since the first descriptions of Esquirol in the nineteenth, the medical community has always been questioned on medical, legal, social or ethical aspects of transsexualism. The aetiology of the trouble is still unknown. In the absence of biological marker, the syndrome of transsexualism can be defined only with clinical criteria. The main differential diagnosis are sexual ambiguities and psychotic disorders. For the specialists, satisfying the patients demand of a surgical and social reassignment still remains the only way to improve their clinical condition and avoid the onset of many dramatic complications. Without any treatment, the evolution of the trouble is chronic, without remission. Longitudinal studies of transsexual patients with a five year follow-up demonstrated subjective improvement in two thirds of the patients and don't find either higher rates of suicides nor psychotic decompensations after surgery and hormonotherapy. Clinical and neuropsychological studies of sexually differentiated cognitive abilities of transsexual patients, before and after hormonotherapy, could allow us in improving the understanding of sexual differences of the brain.

Clinically Significant Enhancement of Voriconazole Efficacy by Moxifloxacin and Gentamicin in Fungal Keratitis.

PubMed

Matoba, Alice Y; Divatia, Mukul K; Arguello, Robert A; Chevez-Barrios, Paty

2018-05-01

To report the effect of topical antibiotics moxifloxacin 0.3% and gentamicin 0.3% on the clinical efficacy of topical antifungal agent voriconazole 1% in cases of culture- or biopsy-proven fungal keratitis. Two cases of fungal keratitis in which the addition of topical moxifloxacin or moxifloxacin and gentamicin led to an improved clinical response to topical voriconazole were reviewed retrospectively. One patient with clinical resistance of his fungal keratitis to both topical voriconazole and natamycin had resolution of his keratitis with the addition of topical moxifloxacin and gentamicin to voriconazole. One patient who had a poor response to topical voriconazole had a dramatic response to the increase of the voriconazole regimen and addition of moxifloxacin. In a subset of patients with fungal keratitis, the addition of topical moxifloxacin 0.3% or moxifloxacin 0.3% and gentamicin 0.3% may enhance the therapeutic effect of topical voriconazole 1%.

Dramatically Improve How and Where Academic Content Is Taught

ERIC Educational Resources Information Center

Hyslop, Alisha

2007-01-01

The fourth recommendation in ACTE's high school reform position statement is to dramatically improve how and where academic content is taught. Even as advanced academic course-taking and high school graduation requirements have increased, student achievement on national benchmarks has remained flat, and college remediation rates continue to…

Dramatic Developments in the Neurosciences Challenge Educators.

ERIC Educational Resources Information Center

Sylwester, Robert

1986-01-01

Recent dramatic developments in brain research and technology suggest that a comprehensive understanding of how the human brain works may soon be within reach. Just as the ability of the medical profession to treat patients improved dramatically with the advent of effective research skills and technology concerning the structure, biochemistry, and…

Brain-controlled muscle stimulation for the restoration of motor function

PubMed Central

Ethier, Christian; Miller, Lee E

2014-01-01

Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional Electrical Stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘Brain Machine Interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

Improvement of a Clinical Score for Necrotizing Fasciitis: ‘Pain Out of Proportion’ and High CRP Levels Aid the Diagnosis

PubMed Central

Siegel, Ekkehard; Hanke, Eric; von Stebut, Esther

2015-01-01

Necrotizing fasciitis (NF) is a rare mono-/polymicrobial skin infection that spreads to underlying tissues. NF is quickly progressing and leads to life threatening situations. Immediate surgical debridement together with i.v. antibiotic administration is required to avoid fatal outcome. Early diagnosis is often delayed due to underestimation or confusion with cellulitis. We now compared the initial clinical and laboratory presentation of NF and cellulitis in detail to assess if a typical pattern can be identified that aids timely diagnosis of NF and avoidance of fatal outcome. 138 different clinical and laboratory features of 29 NF patients were compared to those of 59 age- and gender matched patients with severe erysipelas requiring a subsequent hospitalization time of ≥10 days. Differences in clinical presentation were not obvious; however, NF patients suffered significantly more often from strong pain. NF patients exhibited dramatically elevated CRP levels (5-fold, p>0.001). The overall laboratory risk indicator for necrotizing fasciitis (LRINEC) score was significantly higher in NF patients as compared to cellulitis. However, a modification of the score (alteration of laboratory parameters, addition of clinical parameters) led to a clear improvement of the score with a higher positive predictive value without losing specificity. In summary, clinical differentiation of NF from cellulitis appears to be hard. ‘Pain out of proportion’ may be an early sign for NF. An improvement of the LRINEC score emphasizing only relevant laboratory and clinical findings as suggested may aid the early diagnosis of NF in the future leading to improvement of disease outcome by enabling rapid adequate therapy. PMID:26196941

Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

PubMed

Sturn, Kayla M; Collin, Michael

2016-01-01

Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Clinical image processing engine

NASA Astrophysics Data System (ADS)

Han, Wei; Yao, Jianhua; Chen, Jeremy; Summers, Ronald

2009-02-01

Our group provides clinical image processing services to various institutes at NIH. We develop or adapt image processing programs for a variety of applications. However, each program requires a human operator to select a specific set of images and execute the program, as well as store the results appropriately for later use. To improve efficiency, we design a parallelized clinical image processing engine (CIPE) to streamline and parallelize our service. The engine takes DICOM images from a PACS server, sorts and distributes the images to different applications, multithreads the execution of applications, and collects results from the applications. The engine consists of four modules: a listener, a router, a job manager and a data manager. A template filter in XML format is defined to specify the image specification for each application. A MySQL database is created to store and manage the incoming DICOM images and application results. The engine achieves two important goals: reduce the amount of time and manpower required to process medical images, and reduce the turnaround time for responding. We tested our engine on three different applications with 12 datasets and demonstrated that the engine improved the efficiency dramatically.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis

PubMed Central

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N. K.

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians. PMID:23662237

Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach

PubMed Central

Sahoo, Satya S; Tao, Shiqiang; Parchman, Andrew; Luo, Zhihui; Cui, Licong; Mergler, Patrick; Lanese, Robert; Barnholtz-Sloan, Jill S; Meropol, Neal J; Zhang, Guo-Qiang

2014-01-01

Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy. PMID:25506198

Comparison of Detection Limits of 4th Generation Combination HIV Antigen/Antibody, p24 Antigen and Viral Load Assays on Diverse HIV Isolates.

PubMed

Stone, Mars; Bainbridge, John; Sanchez, Ana M; Keating, Sheila M; Pappas, Andrea; Rountree, Wes; Todd, Chris; Bakkour, Sonia; Manak, Mark; Peel, Sheila A; Coombs, Robert W; Ramos, Eric M; Shriver, M Kathleen; Contestable, Paul; Nair, Sangeetha Vijaysri; Wilson, David H; Stengelin, Martin; Murphy, Gary; Hewlett, Indira; Denny, Thomas N; Busch, Michael P

2018-05-23

Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical 4 th generation antigen-antibody (Ag/Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab alone assays, but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening and next generation assays. Blinded 300 member panels of 20 serially diluted well-characterized antibody negative HIV isolates were distributed to manufacturers and end-user labs to assess relative analytic sensitivity of currently approved and pre-approved clinical HIV 4 th generation Ag/Ab combo or p24 Ag alone immunoassays across diverse subtypes. The limits of virus detection (LODs) were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blinded panel. Based on the proportion of positive results on 300 observations all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half log LODs, illustrating similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo-assays performed poorly. Similar performance of the different commercially available 4 th gen assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next generation pre-clinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while p24 Ag detection by rapid 4 th gen assays performed poorly. Copyright © 2018 American Society for Microbiology.

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

PubMed

Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

Maximizing the clinical utility of antimüllerian hormone testing in women's health

PubMed Central

Leader, Benjamin; Baker, Valerie L.

2014-01-01

Purpose of review To provide an update on the latest clinical applications of serum antimüllerian hormone (AMH) testing with practical approaches to mitigate the impact of significant variability in AMH results. Recent findings Recent studies continue to demonstrate that AMH is the best single serum test for ovarian response management with, at most, a weak-to-moderate age-independent association with live-birth rate and time to conception. Data confirm serum AMH levels improve menopause prediction, monitoring of ovarian damage, and identification of women at risk for several ovary-related disorders such as polycystic ovary syndrome and premature or primary ovarian insufficiency. However, it is now recognized that serum AMH results can have dramatic variability due to common, biologic fluctuations within some individuals, use of hormonal contraceptives or other medications, certain surgical procedures, specimen treatment, assay changes, and laboratory calibration differences. Practical guidelines are provided to minimize the impact of variability in AMH results and maximize the accuracy of clinical decision-making. Summary AMH is an ovarian biomarker of central importance which improves the clinical management of women's health. However, with the simultaneous rapid expansion of AMH clinical applications and recognition of variability in AMH results, consensus regarding the clinical cutpoints is increasingly difficult. Therefore, a careful approach to AMH measurement and interpretation in clinical care is essential. PMID:24978853

Toyota's tips drive dramatic ED improvements.

PubMed

2002-11-01

The Toyota Motor Corp.'s key concepts of allowing workers to make changes, putting the customer first, and reducing waste can have a dramatic impact when implemented in emergency departments. Staff should be empowered to make changes to improve quality. A chain of events should be set in motion for each customer request. Identify and eliminate roadblocks that cause delays.

High-quality cardiopulmonary resuscitation: current and future directions.

PubMed

Abella, Benjamin S

2016-06-01

Cardiopulmonary resuscitation (CPR) represents the cornerstone of cardiac arrest resuscitation care. Prompt delivery of high-quality CPR can dramatically improve survival outcomes; however, the definitions of optimal CPR have evolved over several decades. The present review will discuss the metrics of CPR delivery, and the evidence supporting the importance of CPR quality to improve clinical outcomes. The introduction of new technologies to quantify metrics of CPR delivery has yielded important insights into CPR quality. Investigations using CPR recording devices have allowed the assessment of specific CPR performance parameters and their relative importance regarding return of spontaneous circulation and survival to hospital discharge. Additional work has suggested new opportunities to measure physiologic markers during CPR and potentially tailor CPR delivery to patient requirements. Through recent laboratory and clinical investigations, a more evidence-based definition of high-quality CPR continues to emerge. Exciting opportunities now exist to study quantitative metrics of CPR and potentially guide resuscitation care in a goal-directed fashion. Concepts of high-quality CPR have also informed new approaches to training and quality improvement efforts for cardiac arrest care.

Next-Generation of Allergen-Specific Immunotherapies: Molecular Approaches.

PubMed

Curin, Mirela; Khaitov, Musa; Karaulov, Alexander; Namazova-Baranova, Leyla; Campana, Raffaela; Garib, Victoria; Valenta, Rudolf

2018-06-09

The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy. AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life. Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.

Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

PubMed Central

DiGiusto, DL; Cooper, LJN

2007-01-01

The production of clinical-grade T cells for adoptive immunotherapy has evolved from the ex vivo numerical expansion of tumor-infiltrating lymphocytes to sophisticated bioengineering processes often requiring cell selection, genetic modification and other extensive tissue culture manipulations, to produce desired cells with improved therapeutic potential. Advancements in understanding the biology of lymphocyte signaling, activation, homing and sustained in vivo proliferative potential have redefined the strategies used to produce T cells suitable for clinical investigation. When combined with new technical methods in cell processing and culturing, the therapeutic potential of T cells manufactured in academic centers has improved dramatically. Paralleling these technical achievements in cell manufacturing is the development of broadly applied regulatory standards that define the requirements for the clinical implementation of cell products with ever-increasing complexity. In concert with academic facilities operating in compliance with current good manufacturing practice, the prescribing physician can now infuse T cells with a highly selected or endowed phenotype that has been uniformly manufactured according to standard operating procedures and that meets federal guidelines for quality of investigational cell products. In this review we address salient issues related to the technical, immunologic, practical and regulatory aspects of manufacturing these advanced T-cell products for clinical use. PMID:17943498

ABP 980: promising trastuzumab biosimilar for HER2-positive breast cancer.

PubMed

Paplomata, Elisavet; Nahta, Rita

2018-03-01

Approval of the HER2-targeted antibody trastuzumab dramatically improved outcomes for patients with HER2-positive breast cancer. Multiple trastuzumab biosimilars, including ABP 980, are in clinical development. Biosimilars are not identical to the reference biologic, but exhibit equivalence and safety in analytical and clinical studies. Areas covered: A brief introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed review of ABP 980 preclinical and clinical studies are included. We searched PubMed and 2016-2017 ASCO and ESMO conference proceedings for 'ABP 980' or 'trastuzumab biosimilar'. 'ABP 980 and breast cancer' or 'trastuzumab biosimilar and breast cancer' were used to search clinicaltrials.gov for phase III trials. Analytical studies of ABP 980 pharmacokinetics (PK) or pharmacodynamics (PD), phase I studies of ABP 980 safety and PK/PD, and phase III studies of clinical efficacy vs trastuzumab are included. Expert opinion: Questions remain regarding long-term impact of biosimilars on overall healthcare costs, insurance coverage of multiple approved biosimilars, and extensive clinical safety and efficacy follow-up. By producing a competitive market, trastuzumab biosimilars are anticipated to improve access to standard of care therapies, although real-world evidence remains to be obtained. Increased global access to HER2-targeted therapy may eventually alter the landscape of breast cancer and survival rates.

The Role of Nonphysician Clinicians in the Rapid Expansion of HIV Care in Mozambique

PubMed Central

Sherr, Kenneth; Pfeiffer, James; Mussa, Antonio; Vio, Ferruccio; Gimbel, Sarah; Micek, Mark; Gloyd, Stephen

2017-01-01

The shortage of health workers impedes universal coverage of quality HIV services, especially in those countries hardest hit by the epidemic. The dramatic increase in international aid to scale-up HIV services, including antiretroviral therapy (ART), has highlighted workforce deficiencies and provided an opportunity to strengthen health systems capacity. In Mozambique, a country with a high HIV burden and a staggering workforce deficit, the Ministry of Health looked to past experience in workforce expansion to rapidly build ART delivery capacity, including reliance on existing non-physician clinicians (NPC) to prescribe ART and dramatically increasing the output of NPC training. As a result of responsible task shifting, the number of facilities providing ART tripled during a 6-month period, and patients from disadvantaged areas have access to quality ART services. Because the NPC-driven ART approach is integrated into primary health care, the addition of new clinical staff also promises to improve general health services. PMID:19858931

Coherent Raman Scattering Microscopy in Biology and Medicine.

PubMed

Zhang, Chi; Zhang, Delong; Cheng, Ji-Xin

2015-01-01

Advancements in coherent Raman scattering (CRS) microscopy have enabled label-free visualization and analysis of functional, endogenous biomolecules in living systems. When compared with spontaneous Raman microscopy, a key advantage of CRS microscopy is the dramatic improvement in imaging speed, which gives rise to real-time vibrational imaging of live biological samples. Using molecular vibrational signatures, recently developed hyperspectral CRS microscopy has improved the readout of chemical information available from CRS images. In this article, we review recent achievements in CRS microscopy, focusing on the theory of the CRS signal-to-noise ratio, imaging speed, technical developments, and applications of CRS imaging in bioscience and clinical settings. In addition, we present possible future directions that the use of this technology may take.

Coherent Raman Scattering Microscopy in Biology and Medicine

PubMed Central

Zhang, Chi; Zhang, Delong; Cheng, Ji-Xin

2016-01-01

Advancements in coherent Raman scattering (CRS) microscopy have enabled label-free visualization and analysis of functional, endogenous biomolecules in living systems. When compared with spontaneous Raman microscopy, a key advantage of CRS microscopy is the dramatic improvement in imaging speed, which gives rise to real-time vibrational imaging of live biological samples. Using molecular vibrational signatures, recently developed hyperspectral CRS microscopy has improved the readout of chemical information available from CRS images. In this article, we review recent achievements in CRS microscopy, focusing on the theory of the CRS signal-to-noise ratio, imaging speed, technical developments, and applications of CRS imaging in bioscience and clinical settings. In addition, we present possible future directions that the use of this technology may take. PMID:26514285

[Prostatitis and fertility: the biologist's point of view].

PubMed

Le Foll, N; Pont, J-C; Wolf, J-P; Ziyyat, A; Juillard, J-C; Barraud-Lange, V

2012-09-01

There are two leukocytospermia: the leukocytospermia below 10(6) cells/ml comes from the epididymis. It is physiological, improves sperm quality and ART outcomes and therefore must be respected. Leukocytospermia above 10(6) cells/ml are of prostatic origin and reflect a chronic prostatitis. The results of IVF and ICSI with these sperm are always surprisingly improved when compared to those obtained using semen without leukocytes at all. But this improvement is offset by a dramatic increase in the miscarriage rate. Should we treat this leukocytospermia or its cause? A clinical trial is conducted in Cochin hospital with the PHRC Sigma (Male Genital Track Inflammatory Syndrome) that will help us answer this question. It seems, a priori, that it is better to treat the cause and to respect the leukospermia. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The history of COPD.

PubMed

Petty, Thomas L

2006-01-01

The evolution of knowledge concerning COPD and its components--emphysema, chronic bronchitis, and asthmatic bronchitis--covers 200 years. The stethoscope and spirometer became important early tools in diagnosis and assessment. Spirometry remains the most effective means of identification and assessment of the course of COPD and responses to therapy, and is grossly underused for this purpose. Knowledge of the pathogenesis, course and prognosis, and new approaches to therapy have dramatically improved our understanding of this important clinical entity. Smoking cessation improves the early course of disease. Long-term oxygen improves the length and quality of life in selected patients with hypoxemia. Surgery benefits a select few. Today, COPD is a steadily growing global healthcare problem, with increasing morbidity and mortality. Early identification and prevention, and treatment of emerging stages of disease through smoking cessation and a growing number of bronchoactive drugs promises to change the outcome.

Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

DTIC Science & Technology

2017-09-01

ventilator in order to survive. Use of the ventilator severely limits the quality of life of those injured and dramatically increases the demand for health...care for cervical SCI patients so as to lead to an improved quality of life , better-quality health care management, and improved functional outcomes...mechanical ventilator in order to survive. Use of the ventilator severely limits the quality of life of those injured and dramatically increases the

Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome

PubMed Central

Rim, Min Young; Hong, Junshik; Yo, Inku; Park, Hyeonsu; Chung, Dong Hae; Ahn, Jeong Yeal; Park, Jinny; Kim, Yun Soo; Lee, Jae Hoon

2012-01-01

A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone. PMID:23323115

Tunicamycin enhances the antitumor activity of trastuzumab on breast cancer in vitro and in vivo

PubMed Central

Huang, Shengshi; Zhang, Shu; Wang, Fengshan; Shi, Yikang

2015-01-01

Trastuzumab, a humanized monoclonal antibody targeting HER2, has demonstrated clinical benefits for women with HER2-positive breast cancer; however, trastuzumab resistance remains the biggest clinical challenge. In this study, results showed that tunicamycin, an inhibitor of N-glycosylation, synergistically enhanced the antitumor activity of trastuzumab against HER2-overexpressing breast cancer cells through induction of cell cycle arrest and apoptosis. Combined treatment of tunicamycin with trastuzumab dramatically decreased the expression of EGFR family and its down signaling pathway in SKBR3 and MCF-7/HER2 cells. Tunicamycin dose-dependently inhibited tumor growth in both of SKBR3 xenografts and MCF-7/HER2 xenografts. Optimal tunicamycin without inducing ER stress in liver tissue significantly increased the antitumor effect of trastuzumab in MCF-7/HER2 xenografts. Combinations of trastuzumab with N-glycosylation inhibitors tunicamycin may be a promising approach for improving clinical efficacy of trastuzumab. PMID:26498681

The Diabetic foot: A global threat and a huge challenge for Greece

PubMed Central

Papanas, N; Maltezos, E

2009-01-01

The diabetic foot continues to be a major cause of morbidity, posing a global threat. Substantial progress has been now accomplished in the treatment of foot lesions, but further improvement is required. Treatment options may be classified into established measures (revascularisation, casting and debridement) and new modalities. All therapeutic measures should be provided by specialised dedicated multidisciplinary foot clinics. In particular, the diabetic foot is a huge challenge for Greece. There is a dramatic need to increase the number of engaged foot care teams and their resources throughout the country. It is also desirable to continue education of both physicians and general diabetic population on the magnitude of the problem and on the suitable preventative measures. At the same time, more data on the prevalence and clinical manifestations of the diabetic foot in Greece should be carefully collected. Finally, additional research should investigate feasible ways of implementing current knowledge in everyday clinical practice. PMID:20011082

Anti-Lung-Cancer Activity and Liposome-Based Delivery Systems of β-Elemene

PubMed Central

Chen, Meiwan; Zhang, Jinming; Yu, Siqin; Wang, Shengpeng; Zhang, Zaijun; Chen, Jianqiang; Xiao, Jian; Wang, Yitao

2012-01-01

In the past decade, β-elemene played an important role in enhancing the effects of many anticancer drugs and was widely used in the treatment of different kinds of malignancies and in reducing the side effects of chemotherapy. Further study showed that it is also a promising anti-lung cancer drug. However, the clinical application of β-elemene was limited by its hydrophobic property, poor stability, and low bioavailability. With the development of new excipients and novel technologies, plenty of novel formulations of β-elemene have improved dramatically, which provide a positive perspective in terms of clinical application for β-elemene. Liposome as a drug delivery system shows great advantages over traditional formulations for β-elemene. In this paper, we summarize the advanced progress being made in anti-lung cancer activity and the new liposomes delivery systems of β-elemene. This advancement is expected to improve the level of pharmacy research and provide a stronger scientific foundation for further study on β-elemene. PMID:23243436

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

Technological advances in radiotherapy for cervical cancer.

PubMed

Walsh, Lorraine; Morgia, Marita; Fyles, Anthony; Milosevic, Michael

2011-09-01

To discuss the important technological advances that have taken place in the planning and delivery of both external beam radiotherapy and brachytherapy for patients with locally advanced cervical cancer, and the implications for improved clinical outcomes. Technological advances in external beam radiation treatment and brachytherapy for patients with cervical cancer allow more precise targeting of tumour and relative sparing of surrounding normal organs and tissues. Early evidence is emerging to indicate that these advances will translate into improvements in tumour control and reduced side effects. However, there are patient, tumour and treatment-related factors that can detract from these benefits. Foremost among these is complex, unpredictable and sometimes dramatic internal tumour and normal organ motion during treatment. The focus of current research and clinical development is on tracking internal anatomic change in individual patients and adapting treatment plans as required to assure that optimal tumour coverage and normal tissue sparing is maintained at all times. The success of this approach will depend on clear definitions of target volumes, high resolution daily soft tissue imaging, and new software tools for rapid contouring, treatment planning and quality assurance. Radiation treatment of locally advanced cervical cancer is evolving rapidly, driven by advances in technology, towards more individualized patient care that has the potential to substantially improve clinical outcomes.

Clinical approach of using Onyx via transarterial access in treating tentorial dural arteriovenous fistula.

PubMed

Liu, Chuanghong; Xu, Bin; Song, Donglei; Leng, Bing; Mao, Ying; Gu, Yuxiang; Liao, Yujun

2014-11-01

In this study, based on clinical presentation and angiographic findings, we try to investigate the possibility to do transarterial embolization using Onyx to treat tentorial dural arteriovenous fistula (TDAVF). Particular attention will be given to the relationship between vascular anatomic characteristics and clinical management. We retrospectively reviewed the clinical and radiologic data of 26 patients with TDAVFs, who were treated via transarterial approach using Onyx (including three cases treating with balloon assisting) at our department from January 2005 to April 2010. The total obliterated rate was 85.7, 53.8, and 66.7% in the tentorial marginal, lateral, and medial subtype, respectively. Symptoms were improved significantly in the patients whose fistulas were totally and sub-totally obliterated. The mean follow-up duration was 2.9 years. After operation, patients' symptom was dramatically improved indicated by the decrease of individual modified Rankin scale (MRS). Only one patient suffered from temporary paralysis of cranial nerve (CN) III. All 26 patients were clinically stable and without any relapsed, increased, or new symptoms. All patients had resumed their normal activities until the latest follow-up. Treating the TDAVF via transarterial approach using Onyx maybe a feasible clinical practice. The fistula obliterated rate is highly related to the anatomic characteristic, and high complete obliterated rate can be achieved. Our preliminary results showed that Onyx injection with 'balloon assisting' technique can be helpful in some of the cases.

Posttraumatic syringomyelia associated with heavy weightlifting exercises: case report.

PubMed

Balmaseda, M T; Wunder, J A; Gordon, C; Cannell, C D

1988-11-01

Posttraumatic syringomyelia is a well-recognized late sequel to spinal trauma occurring in 1% to 3.2% of spinal cord injured patients. Its clinical presentation is usually marked by pain, ascending sensory loss, increased muscle weakness, and depressed deep tendon reflexes. The case of a 25-year-old man with C8 complete quadriplegia, who developed a syrinx five years after his initial injury, is presented. This patient kept a log of his daily physical workout which consisted of lifting weights of 50 to 60 pounds with his neck extensors and biceps. The diagnosis was made clinically and confirmed by magnetic resonance imaging. Repeated valsalva maneuvers from daily heavy weightlifting exercises most likely predisposed this patient to the development and extension of his syringomyelia. Dramatic improvement followed surgical placement of a subarachnoid shunt.

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

PubMed

Rockstroh, Jürgen Kurt

2017-04-01

Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

Clinical trials in pediatric neuro-oncology: what is missing and how we can improve.

PubMed

Byer, Lennox; Kline, Cassie; Mueller, Sabine

2016-10-01

Brain tumors are the most common solid tumor in childhood, yet outcomes vary dramatically. High-grade gliomas have dismal outcomes with poor survival. By contrast, low-grade gliomas, have high survival rates, but children suffer from morbidity of tumor burden and therapy-associated side effects. In this article, we discuss how current trial designs often miss the opportunity to include end points beyond tumor response and thus fail to offer complete assessments of therapeutic approaches. Quality of life, neurocognitive function and neurofunctional deficits need to be considered when assessing overall success of a therapy. Herein, we identify specific end points that should be included in the interpretation of clinical trial results and accordingly, offer a more comprehensive approach to treatment decision-making.

Methods for Real-Time PCR-Based Diagnosis of Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia abortus Infections in an Opened Molecular Diagnostic Platform.

PubMed

Opota, Onya; Brouillet, René; Greub, Gilbert; Jaton, Katia

2017-01-01

The advances in molecular biology of the last decades have dramatically improved the field of diagnostic bacteriology. In particular, PCR-based technologies have impacted the diagnosis of infections caused by obligate intracellular bacteria such as pathogens from the Chlamydiacae family. Here, we describe a real-time PCR-based method using the Taqman technology for the diagnosis of Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia abortus infection. The method presented here can be applied to various clinical samples and can be adapted on opened molecular diagnostic platforms.

Physician-executives past, present, and future.

PubMed

Smallwood, K G; Wilson, C N

1992-08-01

The dramatic changes in the United States' health care system during the last decade have sparked increasing interest in physician-executives. These executives, skilled in both clinical medicine and health care management, can be found in hospitals, managed care organizations, group practices, and government institutions. This paper outlines the physician-executive's roles and the development process. The remarkable growth in the number of physician-executives is expected to continue as they demonstrate their abilities to help health care providers expand ambulatory services, facilitate provider-physician relationships and physician recruitment, and lend expertise in quality improvement and risk management issues.

A rare case of Ibuprofen-induced eosinophilic meningitis in a 13-year-old girl.

PubMed

Bansal, Sharad; Gupta, Mukesh; Sharma, Deepak; Bansal, Shweta

2014-01-01

Eosinophilic meningoencephalitis is based on clinical manifestations and microscopic identification of eosinophils present in cerebrospinal fluid (CSF). It is caused by a variety of helminthic infections with most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Many case reports are there in which parasites have been found responsible, but there are rare reports of CSF eosinophilia associated with the use of drugs. We report a case of drug-induced (ibuprofen) eosinophilic meningitis in a healthy female who presented to us with severe headache and improved dramatically after drug withdrawal.

Advances in malaria elimination in Botswana: a dramatic shift to parasitological diagnosis, 2008–2014

PubMed Central

Edwards, J. K.; Motlaleng, M.; Namboze, J.; Butt, W.; Obopile, M.; Mosweunyane, T.; Manzi, M.; Takarinda, K. C.; Owiti, P.

2018-01-01

Background: Malaria elimination requires infection detection using quality assured diagnostics and appropriate treatment regimens. Although Botswana is moving towards malaria elimination, reports of unconfirmed cases may jeopardise this effort. This study aimed to determine the proportion of cases treated for malaria that were confirmed by rapid diagnostic testing (RDT) and/or microscopy. Methods: This was a retrospective descriptive study using routine national data from the integrated disease surveillance and case-based surveillance systems from 2008 to 2014. The data were categorised into clinical and confirmed cases each year. An analysis of the data on cases registered in three districts that reported approximately 70% of all malaria cases was performed, stratified by year, type of reporting health facilities and diagnostic method. Results: During 2008–2014, 50 487 cases of malaria were reported in Botswana, and the proportion of RDT and/or blood microscopy confirmed cases improved from 6% in 2008 to 89% in 2013. The total number of malaria cases decreased by 97% in the same period, then increased by 41% in 2013. Conclusion: This study shows that malaria diagnostic tests dramatically improved malaria diagnosis and consequently reduced the malaria burden in Botswana. The study identified a need to build capacity on microscopy for species identification, parasite quantification and guiding treatment choices. PMID:29713592

Advances in malaria elimination in Botswana: a dramatic shift to parasitological diagnosis, 2008-2014.

PubMed

Moakofhi, K; Edwards, J K; Motlaleng, M; Namboze, J; Butt, W; Obopile, M; Mosweunyane, T; Manzi, M; Takarinda, K C; Owiti, P

2018-04-25

Background: Malaria elimination requires infection detection using quality assured diagnostics and appropriate treatment regimens. Although Botswana is moving towards malaria elimination, reports of unconfirmed cases may jeopardise this effort. This study aimed to determine the proportion of cases treated for malaria that were confirmed by rapid diagnostic testing (RDT) and/or microscopy. Methods: This was a retrospective descriptive study using routine national data from the integrated disease surveillance and case-based surveillance systems from 2008 to 2014. The data were categorised into clinical and confirmed cases each year. An analysis of the data on cases registered in three districts that reported approximately 70% of all malaria cases was performed, stratified by year, type of reporting health facilities and diagnostic method. Results: During 2008-2014, 50 487 cases of malaria were reported in Botswana, and the proportion of RDT and/or blood microscopy confirmed cases improved from 6% in 2008 to 89% in 2013. The total number of malaria cases decreased by 97% in the same period, then increased by 41% in 2013. Conclusion: This study shows that malaria diagnostic tests dramatically improved malaria diagnosis and consequently reduced the malaria burden in Botswana. The study identified a need to build capacity on microscopy for species identification, parasite quantification and guiding treatment choices.

Clinical supervision of allied health professionals in country South Australia: A mixed methods pilot study.

PubMed

Kumar, Saravana; Osborne, Kate; Lehmann, Tanya

2015-10-01

Recent times have witnessed dramatic changes in health care with overt recognition for quality and safety to underpin health care service delivery. In addition to systems-wide focus, the importance of supporting and mentoring people delivering the care has also been recognised. This can be achieved through quality clinical supervision. In 2010, Country Health South Australia Local Health Network developed a holistic allied health clinical governance structure, which was implemented in 2011. This research reports on emergent findings from the evaluation of the clinical governance structure, which included mandating clinical supervision for all allied health staff. A mixed method approach was chosen with evaluation of the impact of clinical supervision undertaken by a psychometrically sound instrument (Manchester Clinical Supervision Scale 26-item version), collected through an anonymous online survey and qualitative data collected through semistructured interviews and focus groups. Overall, 189 allied health professionals responded to the survey. Survey responses indicated allied health professionals recognised the importance of and valued receiving clinical supervision (normative domain), had levels of trust and rapport with, and were supported by supervisors (restorative domain) and positively affected their delivery of care and improvement in skills (formative domain). Qualitative data identified enablers such as profession specific gains, improved opportunities and consistency for clinical supervision and barriers such as persistent organisational issues, lack of clarity (delineation of roles) and communication issues. The findings from this research highlight that while clinical supervision has an important role to play, it is not a panacea for all the ills of the health care system. © 2015 National Rural Health Alliance Inc.

Real-time evaluation of tissue vitality by monitoring of microcirculatory blood flow, HbO2, and mitochondrial NADH redox state

NASA Astrophysics Data System (ADS)

Deutsch, Assaf; Pevzner, Eliyahu; Jaronkin, Alex; Mayevsky, Avraham

2004-06-01

Monitoring of tissue vitality (oxygen supply/demand) in real time is very rare in clinical practice although its use as an early warning alarming system, for clinical care medicine, is very practical. In our previous communication (SPIE 2003) we described the Tissue Spectroscope - TiSpec02, by which tissue microcirculatory blood flow (TBF) and mitochondrial NADH fluorescence were measured using a single light source (390nm). In order to improve the measurement capabilities as well as to decrease dramatically the size and cost of this clinical device, we have changed the TiSpec02 into a multi-wavelength illumination system in the new TiSpec03. In order to measure microcirculatory blood flow by laser Doppler flowmetry we used a 785nm laser diode. For mitochondrial NADH fluorescence measurement we adopted the 370nm LED. For the determination of the oxygenation level of hemoglobin (HbO2) we used the 2-wavelength reflectance technique. This new monitored parameter that was added to the TiSpec03 increases the accuracy of the diagnosis of tissue vitality. The bundle of optical fibers used to connect the tissue to the TiSpec03, was integrated into a special anchoring methodology depending on the monitored tissue or organ. In order to test the performance of the improved TiSpec we have used it in experimental animals brain models exposed to various pathophysiological conditions. Rats and gerbils were anesthetized and the fiber optic probe was located epidurally used dental acrylic cement. During anoxia and ischemia the lack of O2 led to a clear decrease in TBF and HbO2 while NADH shows a large elevation. When brain activation was induced by cortical spreading depression (SD), the elevated O2 consumption was recorded as a large oxidation (decrease) of mitochondrial NADH while TBF increase dramatically. Blood HbO2 was not affected significantly by the SD wave.

Elucidating the nature and mechanism of tic improvement in tourette syndrome: a pilot study.

PubMed

Shprecher, David R; Gannon, Keenan; Agarwal, Nivedita; Shi, Xianfeng; Anderson, Jeffrey S

2014-01-01

For unclear reasons, many Tourette syndrome (TS) children report near-complete tic remission by young adulthood. Immature maturation of brain networks, observed with resting-state functional MRI (rs-fc-MRI) in adolescents and adults with TS, might evolve to a mature pattern in adults who experience tic improvement or remission. We explored the feasibility of testing this hypothesis in our population of young adult TS males, each with prior clinical assessments completed during childhood as part of a separate TS Association Genetics Consortium study. A total of 10 TS males (off tic suppressing drugs for at least 6 months) aged 19-32 years, mean follow-up interval 7.5 (2 to 13) years, and 11 neurologically normal controls were enrolled and underwent 3-Tesla structural and rs-fc-MRI sequences. The mean change in Yale Global Tic Severity Scale (YGTSS) was -31.5% (total) and -26.6% (YGTSS motor+vocal). Two subjects reported resolution of tic-related disability, with drops from mean 45 to 16.5 (YGTSS-total) and 25 to 11.5 (YGTSS motor+vocal.). Rs-fc-MRI revealed significantly increased connectivity between the ipsilateral anterior and mid cingulate cortex and striatum, increased connectivity between local connections, and decreased connectivity between more distant connections; representing an immature connectivity pattern. Similar to previous reports, we found immature patterns of functional connectivity in adult TS subjects. Despite a lack of complete tic remission, two subjects exhibited dramatic drops in tic severity that correlated with tic-related disability improvement. More work is needed to elucidate the mechanism of such dramatic improvement in TS.

Myths and realities of the 80-hour work week.

PubMed

Schenarts, Paul J; Anderson Schenarts, Kimberly D; Rotondo, Michael F

2006-01-01

Myths are so ingrained into cultural traditions that emotion frequently overshadows a rational evaluation of the facts. The reduction in resident work hours has resulted in the formation of several myths. The purpose of this review is to examine the published data on resident work hours to separate out myth from reality. An electronic database was searched for publications related to resident training, work-hours, continuity of care, sleep deprivation, quality of life, patient safety, clinical/operative experience, faculty work hours, and surgical education. Sleep deprivation has been shown to be harmful, and residents played a role in advocating for work-hour limits. Surgical residents have seen a less dramatic improvement in quality of life compared with other disciplines. Work-hour reductions have decreased participation in clinic but have not resulted in a significant decline in clinical or operative exposure. Limiting resident work hours will unlikely result in a decrease health-care cost. Reduction in resident work hours has not resulted in an improvement or deterioration in patient outcome. Reduction of work hours has not increased faculty work hours nor made surgery a more attractive career choice. Despite strongly held opinions, resident work-hour reduction has resulted in little significant change in lifestyle, clinical exposure, patient well-being, faculty work hours, or medical student recruitment.

The importance of imaging strategies for pre-clinical and clinical in vivo distribution of oncolytic viruses

PubMed Central

Pelin, Adrian; Wang, Jiahu; Bell, John; Le Boeuf, Fabrice

2017-01-01

Oncolytic viruses (OVs) are an emergent and unique therapy for cancer patients. Similar to chemo- and radiation therapy, OV can lyse (kill) cancer cell directly. In general, the advantages of OVs over other treatments are primarily: a higher safety profile (as shown by less adverse effects), ability to replicate, transgene(s) delivery, and stimulation of a host’s immune system against cancer. The latter has prompted successful use of OVs with other immunotherapeutic strategies in a synergistic manner. In spite of extended testing in pre-clinical and clinical setting, using biologically derived therapeutics like virus always raises potential concerns about safety (replication at non-intended locations) and bio-availability of the product. Recent advent in in vivo imaging techniques dramatically improves the convenience of use, quality of pictures, and amount of information acquired. Easy assessing of safety/localization of the biotherapeutics like OVs became a new potential weapon in the physician’s arsenal to improve treatment outcome. Given that OVs are typically replicating, in vivo imaging can also track virus replication and persistence as well as precisely mapping tumor tissues presence. This review discusses the importance of imaging in vivo in evaluating OV efficacy, as well as currently available tools and techniques. PMID:29637059

Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome?

PubMed

Mekinian, Arsene; Costedoat-Chalumeau, Nathalie; Masseau, Agathe; Tincani, Angela; De Caroli, Sara; Alijotas-Reig, Jaume; Ruffatti, Amelia; Ambrozic, Ales; Botta, Angela; Le Guern, Véronique; Fritsch-Stork, Ruth; Nicaise-Roland, Pascale; Carbonne, Bruno; Carbillon, Lionel; Fain, Olivier

2015-01-01

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

Drug Delivery in Cancer Therapy, Quo Vadis?

PubMed

Lu, Zheng-Rong; Qiao, Peter

2018-03-22

The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

A combined hands-on teaching programme and clinical pathway focused on pleural ultrasound and procedure supervision transforms pleural procedure outcomes.

PubMed

Edwards, Timothy; Cook, Alistair; Salamonsen, Matthew; Bashirzadeh, Farzad; Fielding, David

2017-11-01

Management of pleural effusions is a common diagnostic and management problem. We reviewed the outcomes from pleural procedures after the instigation of pleural effusion management guidelines, focusing on pleural ultrasound and a hands-on teaching programme followed by procedure supervision that enabled many operators to perform such procedures. This is a retrospective analysis of all procedures performed for pleural effusions on medical patients. Outcomes were assessed prior to the instigation of pleural effusion management guidelines (pleural pathway) and hands-on teaching (January 2010 to June 2011) and following these interventions (January 2012 to June 2013). A total of 171 procedures involving 129 patients (pre-pathway group) and 146 procedures involving 115 patients (post-pathway group) was analysed. The rate of complications prior to the pleural pathway was 22.2% (38 of 171 procedures). Following the pathway, the rate of complications declined to 7.5% (11 of 146 procedures, P < 0.003). The use of pleural ultrasound increased dramatically (72.5 vs 90.2%). The number of patients who underwent repeated procedures (defined as ≥3) reduced dramatically (21 vs 7, P < 0.01). This improvement occurred using many supervised operators who completed the hands-on teaching programme (n = 32) and followed the pleural pathway (127 of 146 procedures). The instigation of a clinical pathway focused on the use of bedside pleural ultrasound, and teaching of drainage techniques with procedure supervision vastly improved patient outcomes. This not only allowed better quality of care for patients, it also provided the acquisition of new skills to medical staff, not limiting these skills to specialised staff. © 2017 Royal Australasian College of Physicians.

Enhanced recovery after surgery: Current research insights and future direction

PubMed Central

Abeles, Aliza; Kwasnicki, Richard Mark; Darzi, Ara

2017-01-01

Since the concept of enhanced recovery after surgery (ERAS) was introduced in the late 1990s the idea of implementing specific interventions throughout the peri-operative period to improve patient recovery has been proven to be beneficial. Minimally invasive surgery is an integral component to ERAS and has dramatically improved post-operative outcomes. ERAS can be applicable to all surgical specialties with the core generic principles used together with added specialty specific interventions to allow for a comprehensive protocol, leading to improved clinical outcomes. Diffusion of ERAS into mainstream practice has been hindered due to minimal evidence to support individual facets and lack of method for monitoring and encouraging compliance. No single outcome measure fully captures recovery after surgery, rather multiple measures are necessary at each stage. More recently the pre-operative period has been the target of a number of strategies to improve clinical outcomes, described as prehabilitation. Innovation of technology in the surgical setting is also providing opportunities to overcome the challenges within ERAS, e.g., the use of wearable activity monitors to record information and provide feedback and motivation to patients peri-operatively. Both modernising ERAS and providing evidence for key strategies across specialties will ultimately lead to better, more reliable patient outcomes. PMID:28289508

Objective evidence for the use of polylactic acid implants in HIV-associated facial lipoatrophy using three-dimensional surface laser scanning and psychological assessment.

PubMed

Ong, J; Clarke, A; White, P; Johnson, M A; Withey, S; Butler, P E M

2009-12-01

The advent of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of people infected with human immunodeficiency virus (HIV). Although patients often have excellent disease control with these combinations of antiretrovirals, they are at risk for the multiple toxicities associated with these drugs. Facial lipoatrophy is a particularly distressing complication of some HAART regimes. This disfigurement can lead to significant psychosocial stress, resulting in decreased treatment compliance. Polylactic acid (PLA) facial implants provide a potential method of restoring a normal appearance. One hundred consecutive patients had a course of PLA facial implants. All patients were assessed clinically and had photographs, facial surface laser scans and completed psychological questionnaires throughout the course of treatment. After a mean of 4.85 treatments per patient, there were improvements in all measures. The mean clinical scores improved from a moderate-severe grade to none-mild grade after treatment. Three-dimensional (3D) laser surface scans showed a volume increase of 2.81 cc over the treated area of the cheek. There were significant improvements in all of the psychological measures. This study shows clear objective evidence of the psychological and physical benefit of PLA implants in HIV-associated facial lipodystrophy.

Finding the Why, Changing the How: Improving the Mental Health of Medical Students, Residents, and Physicians.

PubMed

Slavin, Stuart J; Chibnall, John T

2016-09-01

The poor mental health of residents, characterized by high rates of burnout, depression, and suicidal ideation, is a growing concern in graduate medical education. Research is needed to gain a deeper understanding of the sources of distress as well as the sources of sustenance in residency training. The study by Mata and colleagues contributes significantly to this understanding. In addition to this line of research, however, studies are needed that assess the impact of interventions to help residents deal more effectively with the stress of training and find meaning in their work. Given the stresses of residency training, this approach may not make a dramatic difference in mental health outcomes. Efforts directed at changing the educational and clinical environments are also needed to reduce unnecessary stressors and create more positive settings for learning and clinical care. Since 2011, Saint Louis University School of Medicine has been pursuing a multipronged strategy to address these issues in the preclinical years. These efforts have led to dramatic decreases in depression and anxiety symptoms in students. An essential component of these interventions is the ongoing measurement of mental health outcomes across all four years of the curriculum. Leaders of residency programs, medical schools, and hospitals need to have the courage to measure these kinds of outcomes to spur change and track the efficacy of programs.

Deanol acetamidobenzoate (Deaner) in tardive dyskinesia.

PubMed

Stafford, J R; Fann, W E

1977-12-01

A total of twenty-nine patients have thus far been treated with deanol in various dosage levels for periods ranging from five to thirty days. Clinical response has been pronounced, even dramatic, in seven patients, moderate but significant in nine patients, and slight to insignificant in thirteen others. Videotape rating and quantitative accelerometry, to the extent that they constitute novel and stress-inducing experiences may not be representative of global clinical changes. Deanol did not produce the anticipated elevation in choline levels postulated to be one mechanism of its action. The failure of deanol to achieve this effect may most probably be attributed to interval after last dose, to inadequate level of deanol or to some alteration in choline metabolism in the presence of deanol. The etiology of tardive dyskinesia at biochemical and structural levels is complex. For some patients improvement has been dramatic and clearly associated with deanol. Others appear to exhibit minimal response which cannot be differentiated from placebo or environmental effects. Our present strategy, in common with that of other authors includes the administration of a "challenge" dose of rapid acting injectable cholinomimetic agents (e.g. physostigmine) and dopamine-blocking agents (e.g. haloperidol) with placebo controls. In this manner therapy may be more rationally selected for long-term use and may logically include deanol. The correlation of such predictive challenges with response to long-term treatment is an area for much more well controlled study.

Treatment with teriparatide in a patient with pregnancy-associated osteoporosis.

PubMed

Hellmeyer, Lars; Boekhoff, Jelena; Hadji, Peyman

2010-10-01

The decrease of BMD during a physiological pregnancy can in rare cases be intensified and lead to dramatic microarchitectural changes, which causes an increase incidence of fractures, preferably at the spine. This dramatic clinical picture is called pregnancy-associated osteoporosis. We present the case of a 40-year-old woman (gravida IV, para II) with acute back pain right after delivery due to four fractures of the spine. The diagnosis was confirmed by dual-energy X-ray absorptiometry measurement result (T-score -4.1 SD (0.598 g/cm(2)) at the lumbar spine (L1-L4), T-score -1.5 SD (0.759 g/cm(2)) at the total hip). Due to the severity of symptoms, a therapy with teriparatide (20 mg daily) was started for a period of 18 months. After end of therapy, the T-score had significantly increased at the lumbar spine as well as at the hip (T-score of -2.1 (0.813 g/cm(2)) and -0.6 (0.864 g/cm(2)), respectively. The relative increase of BMD at the spine and total hip was 36% and 13.8%, respectively. Our report demonstrates the successful use of teriparatide underlined by the increase of bone mineral density and the improvement of clinical symptoms in a case of severe pregnancy-associated osteoporosis for the first time.

Biological Strategies for Improved Osseointegration and Osteoinduction of Porous Metal Orthopedic Implants

PubMed Central

Riester, Scott M.; Bonin, Carolina A.; Kremers, Hilal Maradit; Dudakovic, Amel; Kakar, Sanjeev; Cohen, Robert C.; Westendorf, Jennifer J.

2015-01-01

The biological interface between an orthopedic implant and the surrounding host tissue may have a dramatic effect upon clinical outcome. Desired effects include bony ingrowth (osseointegration), stimulation of osteogenesis (osteoinduction), increased vascularization, and improved mechanical stability. Implant loosening, fibrous encapsulation, corrosion, infection, and inflammation, as well as physical mismatch may have deleterious clinical effects. This is particularly true of implants used in the reconstruction of load-bearing synovial joints such as the knee, hip, and the shoulder. The surfaces of orthopedic implants have evolved from solid-smooth to roughened-coarse and most recently, to porous in an effort to create a three-dimensional architecture for bone apposition and osseointegration. Total joint surgeries are increasingly performed in younger individuals with a longer life expectancy, and therefore, the postimplantation lifespan of devices must increase commensurately. This review discusses advancements in biomaterials science and cell-based therapies that may further improve orthopedic success rates. We focus on material and biological properties of orthopedic implants fabricated from porous metal and highlight some relevant developments in stem-cell research. We posit that the ideal primary and revision orthopedic load-bearing metal implants are highly porous and may be chemically modified to induce stem cell growth and osteogenic differentiation, while minimizing inflammation and infection. We conclude that integration of new biological, chemical, and mechanical methods is likely to yield more effective strategies to control and modify the implant–bone interface and thereby improve long-term clinical outcomes. PMID:25348836

Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L

2018-03-01

Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.

The Audible Pop from Thoracic Spine Thrust Manipulation and Its Relation to Short-Term Outcomes in Patients with Neck Pain

PubMed Central

Cleland, Joshua A.; Flynn, Timothy W.; Childs, John D.; Eberhart, Sarah

2007-01-01

Clinicians routinely consider the success of a thrust manipulation technique based on the presence or absence of an audible pop despite the lack of evidence suggesting that this pop is associated with improved outcomes. The purpose of this study was to determine the relationship between the number of audible pops with thoracic spinal manipulation and improvement in pain and function in patients with mechanical neck pain. In this prospective cohort study, 78 patients referred to physical therapy with mechanical neck pain underwent a standardized examination and thoracic spine manipulation treatment protocol. All patients were treated with a total of 6 thrust manipulation techniques directed to the thoracic spine followed by a basic cervical range of motion exercise. The treating clinician recorded the presence or absence of a pop during each manipulation. Outcomes were assessed at a 2–4 day follow-up with an 11-point numeric pain rating (NPRS), the Neck Disability Index, the patient Global Rating of Change (GROC), and measurements of cervical range of motion (CROM). The relationship between the number of pops and change scores for pain, disability, and CROM was first examined using Pearson correlation coefficients. Individuals were then categorized as having received ≤3 or >3 pops. Repeated measures analyses of variance were used to examine whether achievement of >3 pops resulted in improved outcome. Seventy-eight patients with a mean age of 42 (SD 11.3) years participated in the study. Pearson correlation coefficients revealed no significant correlation existed between the number of pops and outcomes with the exception of 3 of the 6 CROM measurements, which were inversely related. There was no significant interaction for group X time for any of the dependent measures (P>0.05). The odds ratio for patients experiencing dramatic improvement was in favor of the group experiencing ≤3 pops but this was not clinically meaningful (1.3: 95% CI 0.46, 3.7). The results of this analysis provide preliminary evidence for the hypothesis that there is no relationship between the number of audible pops during thoracic spine thrust manipulation and clinically meaningful improvements in pain, disability, or CROM in patients with mechanical neck pain. Additionally, a greater number of audible pops experienced was not associated with a dramatic improvement with manipulation treatment. PMID:19066662

Carbon Nanostructures in Bone Tissue Engineering

PubMed Central

Perkins, Brian Lee; Naderi, Naghmeh

2016-01-01

Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

Building electronic data infrastructure for comparative effectiveness research: accomplishments, lessons learned and future steps.

PubMed

Randhawa, Gurvaneet S

2014-11-01

There are large gaps in our knowledge on the potential impact of diagnostics and therapeutics on outcomes of patients treated in the real world. Comparative effectiveness research aims to fill these gaps to maximize effectiveness of these interventions. Health information technology has the potential to dramatically improve the practice of medicine and of research. This is an overview of about US$100 million of American Recovery and Reinvestment Act investment in 12 projects managed by the Agency for Healthcare Research and Quality to build an electronic clinical data infrastructure that connects research with healthcare delivery. The achievements and lessons learned from these projects provided a foundation for the National Patient-Centered Clinical Research Network (PCORnet)and will help to guide future infrastructure development needed to build an efficient, scalable and sustainable learning health system.

Outcomes research in evaluating the benefit of health care technology

NASA Astrophysics Data System (ADS)

Fendrick, A. Mark

1995-10-01

Although medical innovation can reduce morbidity and mortality associated with diseases or their treatments, in most instances new interventions tend to increase the amount of resources expended on health care services. In this era of increasing cost consciousness, there is a perceived tension between the desire to improve health outcomes and the necessity to control the growth of health care costs. The dramatic changes in the organization, financing, and delivery of health care services, make it no longer acceptable to provide any and all services to every individual with only a remote probability of clinical benefit. An incentive structure which rewards the practice of cost-effective medical care is rapidly replacing the 'technological imperative' of decades past. As the expansion towards managed care continues, increasing scrutiny will be paid to the clinical and cost implications of our medical interventions.

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

PubMed

Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

2016-01-01

The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

PubMed Central

Wang, Mingyi; Shah, Ajay M

2015-01-01

The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

A formative evaluation of a nurse practitioner-led interprofessional geriatric outpatient clinic.

PubMed

Hansen, Kevin T; McDonald, Cheryl; O'Hara, Sue; Post, Leslie; Silcox, Susan; Gutmanis, Iris A

2017-07-01

The number of older adults with multiple complex comorbidities and frailty is expected to increase dramatically in the coming decades, which will necessitate a concomitant increase in the need for skilled clinicians who are able to manage complex geriatric needs. Many physicians, however, lack the required formal training, often leading to long wait-lists for specialist clinics. Yet, clinics led by non-physician professionals specialising in geriatric care could decrease these delays. This article describes the development and evaluation of a nurse practitioner-led interprofessional geriatric outpatient clinic (Inter-D Clinic). A combination of semi-structured clinician interviews, post-clinic follow-up phone calls, satisfaction surveys, and information from the hospital workload management system served as data sources for this formative programme evaluation. Between January 2013 and December 2014, 293 patients were seen in the clinic with the majority being referred for either memory issues (49%) or functional decline (35%). The clinic assessment frequently uncovered other issues, which led to guidance around falls prevention, improved nutrition, medication management, and referrals to available community supports. Both patients and referring physicians were very satisfied with this model of care, which is likely transferable to other locations provided the needed clinical expertise and community support services are available.

Hyperammoniemic coma in a patient with ureterosigmoidostomy and normal liver function.

PubMed

Van Laethem, J L; Gay, F; Franck, N; Van Gossum, A

1992-11-01

Hyperammoniemic encephalopathy has been reported after ureterosigmoidostomy. Its development is related to a problem of bacterial overgrowth and, most often, is favored by the presence of an underlying liver dysfunction. We report the case of a 43-year-old woman with a ureterosigmoidostomy done 28 years earlier who developed hyperammoniemic coma induced by an acute rectocolitis and in the absence of any detectable liver dysfunction. Neither administration of Lactilol and neomycin nor rectal tube drainage were effective; systemic antimicrobial therapy effective against the urease-producing gram-negative bacilli was required and led to a decrease in serum ammonia levels and a dramatic clinical improvement.

Novel Highly Porous Metal Technology in Artificial Hip and Knee Replacement: Processing Methodologies and Clinical Applications

NASA Astrophysics Data System (ADS)

Muth, John; Poggie, Matthew; Kulesha, Gene; Michael Meneghini, R.

2013-02-01

Hip and knee replacement can dramatically improve a patient's quality of life through pain relief and restored function. Fixation of hip and knee replacement implants to bone is critical to the success of the procedure. A variety of roughened surfaces and three-dimensional porous surfaces have been used to enhance biological fixation on orthopedic implants. Recently, highly porous metals have emerged as versatile biomaterials that may enhance fixation to bone and are suitable to a number of applications in hip and knee replacement surgery. This article provides an overview of several processes used to create these implant surfaces.

Cogan's syndrome mimicking acute Lyme arthritis.

PubMed

Schwegmann, J P; Enzenauer, R J

1995-05-01

A pediatric case of Cogan's syndrome mimicking acute Lyme arthritis is described. A 12-year-old black boy was admitted to the pediatric service for presumed right knee septic arthritis. Symptoms included acute pain and swelling with decreased range-of-motion. Although the patient's right knee symptoms and positive Lyme serology were consistent with a diagnosis of Lyme arthritis, the presence of sensorineural hearing loss and interstitial keratitis with inflammatory arthritis suggested a diagnosis of Cogan's syndrome. Subsequent Western blot analysis was negative for Borrelia burgdorferi antigens. The patient had dramatic clinical improvement of musculoskeletal and ophthalmologic complaints shortly after receiving high-dose corticosteroids, although residual sensorineural hearing loss persisted.

Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)

PubMed Central

Gao, Wenqing; Dalton, James T.

2007-01-01

Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5α-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies. PMID:17331889

Developmental improvements in dynamic control of fingertip forces last throughout childhood and into adolescence

PubMed Central

Dayanidhi, Sudarshan; Hedberg, Åsa; Forssberg, Hans

2013-01-01

While it is clear that the development of dexterous manipulation in children exhibits dramatic improvements over an extended period, it is difficult to separate musculoskeletal from neural contributors to these important functional gains. This is in part due to the inability of current methods to disambiguate improvements in hand strength from gains in finger dexterity (i.e., the dynamic control of fingertip force vectors at low magnitudes). We adapted our novel instrumentation to evaluate finger dexterity in 130 typically developing children between the ages of 4 and 16 yr. We find that finger dexterity continues to develop well into late adolescence and musculoskeletal growth and strength are poorly correlated with the improvements in dexterity. Importantly, because these behavioral results seem to mirror the known timelines of neuroanatomical development up to adolescence, we speculate that they reflect the functional benefits of such continual neural maturation. This novel perspective now enables the systematic study of the functional roles of specific neuroanatomical structures and their connectivity, maturity, and plasticity. Moreover, the temporal dynamics of the fingertip force vectors shows improvements in stability that provide a novel way to look at the maturation of finger control. From a clinical perspective, our results provide a practical means to chart functional development of dexterous manipulation in typically developing children and could be adapted for clinical use and for use in children with developmental disorders. PMID:23864371

Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group.

PubMed

Rodeghiero, Francesco; Stasi, Roberto; Gernsheimer, Terry; Michel, Marc; Provan, Drew; Arnold, Donald M; Bussel, James B; Cines, Douglas B; Chong, Beng H; Cooper, Nichola; Godeau, Bertrand; Lechner, Klaus; Mazzucconi, Maria Gabriella; McMillan, Robert; Sanz, Miguel A; Imbach, Paul; Blanchette, Victor; Kühne, Thomas; Ruggeri, Marco; George, James N

2009-03-12

Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.

Immunomodulatory drugs in multiple myeloma: mechanisms of action and clinical experience

PubMed Central

Holstein, Sarah A.; McCarthy, Philip L.

2017-01-01

Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis. PMID:28205024

Comparisons between MCNP, EGS4 and experiment for clinical electron beams.

PubMed

Jeraj, R; Keall, P J; Ostwald, P M

1999-03-01

Understanding the limitations of Monte Carlo codes is essential in order to avoid systematic errors in simulations, and to suggest further improvement of the codes. MCNP and EGS4, Monte Carlo codes commonly used in medical physics, were compared and evaluated against electron depth dose data and experimental backscatter results obtained using clinical radiotherapy beams. Different physical models and algorithms used in the codes give significantly different depth dose curves and electron backscattering factors. The default version of MCNP calculates electron depth dose curves which are too penetrating. The MCNP results agree better with experiment if the ITS-style energy-indexing algorithm is used. EGS4 underpredicts electron backscattering for high-Z materials. The results slightly improve if optimal PRESTA-I parameters are used. MCNP simulates backscattering well even for high-Z materials. To conclude the comparison, a timing study was performed. EGS4 is generally faster than MCNP and use of a large number of scoring voxels dramatically slows down the MCNP calculation. However, use of a large number of geometry voxels in MCNP only slightly affects the speed of the calculation.

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

PubMed

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

The impact of HIV infection on society's perception of clinical trials.

PubMed

Levine, R J

1994-06-01

All international codes of research ethics and virtually all national legislation and regulation in the field of research involving human subjects project an attitude of protectionism. Written with the aim of avoiding a repetition of atrocities like those committed by the Nazi physician-researchers, calamities like the thalidomide experience, or ethical violations like those of the Tuskegee syphilis study, their dominant concerns are the protection of individuals from injury and from exploitation. In recent years, however, society's perception of clinical research has shifted dramatically. Now, largely as a consequence of the efforts of the AIDS activists, clinical research is widely perceived as benign and beneficial. Although this shift in attitude has resulted in some important improvements in research policies and practices, this new perception is just as wrong-headed as was the earlier excessive protectionism. It is necessary to maintain a balanced perspective; our policies should encourage the conduct of ethical research while maintaining the vigilance necessary to safeguard the rights and welfare of the subjects.

An Ocular Protein Triad Can Classify Four Complex Retinal Diseases

NASA Astrophysics Data System (ADS)

Kuiper, J. J. W.; Beretta, L.; Nierkens, S.; van Leeuwen, R.; Ten Dam-van Loon, N. H.; Ossewaarde-van Norel, J.; Bartels, M. C.; de Groot-Mijnes, J. D. F.; Schellekens, P.; de Boer, J. H.; Radstake, T. R. D. J.

2017-01-01

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.

2014-07-15

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local diseasemore » control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.« less

Implementation of Hospital Computerized Physician Order Entry Systems in a Rural State: Feasibility and Financial Impact

PubMed Central

Ohsfeldt, Robert L.; Ward, Marcia M.; Schneider, John E.; Jaana, Mirou; Miller, Thomas R.; Lei, Yang; Wakefield, Douglas S.

2005-01-01

Objective The aim of this study was to estimate the costs of implementing computerized physician order entry (CPOE) systems in hospitals in a rural state and to evaluate the financial implications of statewide CPOE implementation. Methods A simulation model was constructed using estimates of initial and ongoing CPOE costs mapped onto all general hospitals in Iowa by bed quantity and current clinical information system (CIS) status. CPOE cost estimates were obtained from a leading CPOE vendor. Current CIS status was determined through mail survey of Iowa hospitals. Patient care revenue and operating cost data published by the Iowa Hospital Association were used to simulate the financial impact of CPOE adoption on hospitals. Results CPOE implementation would dramatically increase operating costs for rural and critical access hospitals in the absence of substantial costs savings associated with improved efficiency or improved patient safety. For urban and rural referral hospitals, the cost impact is less dramatic but still substantial. However, relatively modest benefits in the form of patient care cost savings or revenue enhancement would be sufficient to offset CPOE costs for these larger hospitals. Conclusion Implementation of CPOE in rural or critical access hospitals may depend on net increase in operating costs. Adoption of CPOE may be financially infeasible for these small hospitals in the absence of increases in hospital payments or ongoing subsidies from third parties. PMID:15492033

Ternary Surface Monolayers for Ultrasensitive (Zeptomole) Amperometric Detection of Nucleic-Acid Hybridization without Signal Amplification

PubMed Central

Wu, Jie; Campuzano, Susana; Halford, Colin; Haake, David A.; Wang, Joseph

2010-01-01

A ternary surface monolayer, consisting of co-assembled thiolated capture probe (SHCP) mercaptohexanol (MCH) and dithiothreitol (DTT), is shown to offer dramatic improvements in the signal-to-noise characteristics of electrochemical DNA hybridization biosensors based on common self-assembled monolayers (SAMs). Remarkably low detection limits down to 40 zmole (in 4 μL samples) as well as only 1 CFU E. coli per sensor are thus obtained without any additional amplification step in connection to the commonly used horseradish peroxidase/3,3′,5,5′-tetramethylbenzidine (HRP/TMB) system. Such dramatic improvements in the detection limits (compared to common binary alkanethiol interfaces and to most electrochemical DNA sensing strategies without target or signal amplification) are attributed primarily to the remarkably higher resistance to non-specific adsorption. This reflects the highly compact layer (with lower pinhole density) produced by the coupling of the cyclic- and linear-configuration ‘backfillers’ that leads to a remarkably low background noise even in the presence of complex sample matrices. A wide range of surface compositions have been investigated and the ternary mixed monolayer has been systematically optimized. Detailed impedance spectroscopy and cyclic voltammetric studies shed useful insights into the surface coverage. The impressive sensitivity and high specificity of the simple developed methodology indicate great promise for a wide range of nucleic acid testing, including clinical diagnostics, biothreat detection, food safety and forensic analysis. PMID:20883023

Ternary surface monolayers for ultrasensitive (zeptomole) amperometric detection of nucleic acid hybridization without signal amplification.

PubMed

Wu, Jie; Campuzano, Susana; Halford, Colin; Haake, David A; Wang, Joseph

2010-11-01

A ternary surface monolayer, consisting of coassembled thiolated capture probe, mercaptohexanol and dithiothreitol, is shown to offer dramatic improvements in the signal-to-noise characteristics of electrochemical DNA hybridization biosensors based on common self-assembled monolayers. Remarkably low detection limits down to 40 zmol (in 4 μL samples) as well as only 1 CFU Escherichia coli per sensor are thus obtained without any additional amplification step in connection to the commonly used horseradish peroxidase/3,3',5,5'-tetramethylbenzidine system. Such dramatic improvements in the detection limits (compared to those of common binary alkanethiol interfaces and to those of most electrochemical DNA sensing strategies without target or signal amplification) are attributed primarily to the remarkably higher resistance to nonspecific adsorption. This reflects the highly compact layer (with lower pinhole density) produced by the coupling of the cyclic- and linear-configuration "backfillers" that leads to a remarkably low background noise even in the presence of complex sample matrixes. A wide range of surface compositions have been investigated, and the ternary mixed monolayer has been systematically optimized. Detailed impedance spectroscopy and cyclic voltammetric studies shed useful insights into the surface coverage. The impressive sensitivity and high specificity of the simple developed methodology indicate great promise for a wide range of nucleic acid testing, including clinical diagnostics, biothreat detection, food safety, and forensic analysis.

The role of neuropsychology in UK pediatric HIV care: Relevance to clinical practice and research.

PubMed

Freeman, Anita

2017-11-01

There has been a dramatic improvement in the survival of children with perinatally-acquired HIV (PHIV) following the introduction of effective treatment in 1990s. The care for children living with PHIV is now focused on more accurately understanding the effects of both HIV and HIV treatment on the developing body and brain. An evaluation of current HIV neuroimaging, and neurocognitive research, when combined with clinical experience in the area of HIV, could help to inform United Kingdom (UK) PHIV service provision. This paper argues that an understanding from a neuropsychological perspective will help these young people to optimize their health, quality of life, and future functioning. The aim of the paper is to bring together research and clinical understanding of HIV and its treatment effects on the developing brain, together with an understanding of other potential neurological risk factors. It is argued here that there is a need for targeted neuropsychology assessment and preventative interventions, supported by clinical and preliminary research on the neurocognitive effects of HIV and its treatments.

High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need

PubMed Central

Cimmino, Giovanni; Ciccarelli, Giovanni; Morello, Alberto; Ciccarelli, Michele; Golino, Paolo

2015-01-01

Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies. PMID:26535185

The place of targeted therapies in the management of non-small cell bronchial carcinoma. Molecular markers as predictors of tumor response and survival in lung cancer.

PubMed

Rosell, R; Moran, T; Fernanda Salazar, M; Mendez, P; De Aguirre, I; Ramirez, J-L; Isla, D; Cobo, M; Camps, C; Lopez-Vivanco, G; Alberola, V; Taron, M

2006-11-01

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.

Rapid Improvement of Glycemic Control in Type 2 Diabetes Using Weekly Intensive Multifactorial Interventions: Structured Glucose Monitoring, Patient Education, and Adjustment of Therapy—A Randomized Controlled Trial

PubMed Central

Rodbard, David; Zanella, Maria Teresa

2011-01-01

Abstract Background We evaluated intensive intervention in poorly controlled patients with type 2 diabetes mellitus involving weekly clinic visits and adjustment of therapy with analysis of three seven-point glucose profiles and intervention from an interdisciplinary staff. Methods Sixty-three patients were randomized to an intensive treatment group that obtained self-monitoring of blood glucose (SMBG) profiles (six or seven values per day, 3 days/week) and were seen in the clinic at Weeks 1–6 and 12. SMBG results were downloaded, analyzed using Accu-Chek® 360° software (Roche Diagnostics, Indianapolis, IN), and used to adjust therapy. Control group subjects obtained glucose profiles and had clinic visits only at Weeks 0, 6, and 12. Results There were highly statistically significant improvements in the intensive treatment group compared with the control group between Weeks 0 and 6 with greater reductions in weekly mean glycemia (WMG) (−76.7±8.9 mg/dL vs. −20.5±8.1 mg/dL), glycemic variability (SD) (−16.3±3.1 mg/dL vs. −5.0±3.1 mg/dL), and glycated hemoglobin (−1.82±0.16% vs. −0.66±0.22%) without significant changes in frequency of hypoglycemia or weight. Improvements were sustained in the intensive treatment group through Week 12. A minimal but statistically significant degree of improvement was seen in the control group at Week 12. Conclusions This short-term pilot study of an intensive monitoring, educational, and pharmacological interventions program resulted in dramatic improvement of glycemic control within 6 weeks, and these effects are sustained through Week 12. SMBG glucose profiles, calculation of WMG and SD, and graphical displays of glucose data can improve the effectiveness of adjustment of therapy at weekly clinic visits when combined with intensive support from a multidisciplinary team. PMID:21751888

CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results.

PubMed

Till, Brian G; Jensen, Michael C; Wang, Jinjuan; Qian, Xiaojun; Gopal, Ajay K; Maloney, David G; Lindgren, Catherine G; Lin, Yukang; Pagel, John M; Budde, Lihua E; Raubitschek, Andrew; Forman, Stephen J; Greenberg, Philip D; Riddell, Stanley R; Press, Oliver W

2012-04-26

Cellular immune responses have the potential to elicit dramatic and sustained clinical remissions in lymphoma patients. Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with costimulatory domains exhibit improved activity against tumors. We conducted a pilot clinical trial testing a "third-generation" CD20-specific CAR with CD28 and 4-1BB costimulatory domains in patients with relapsed indolent B-cell and mantle cell lymphomas. Four patients were enrolled, and 3 received T-cell infusions after cyclophosphamide lymphodepletion. Treatment was well tolerated, although one patient developed transient infusional symptoms. Two patients without evaluable disease remained progression-free for 12 and 24 months. The third patient had an objective partial remission and relapsed at 12 months after infusions. Modified T cells were detected by quantitative PCR at tumor sites and up to 1 year in peripheral blood, albeit at low levels. No evidence of host immune responses against infused cells was detected. In conclusion, adoptive immunotherapy with CD20-specific T cells was well tolerated and was associated with antitumor activity. We will pursue alternative gene transfer technologies and culture conditions in future studies to improve CAR expression and cell production efficiency.

Quantification of Peptides from Immunoglobulin Constant and Variable Regions by Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry for Assessment of Multiple Myeloma Patients

PubMed Central

Remily-Wood, Elizabeth R.; Benson, Kaaron; Baz, Rachid C.; Chen, Y. Ann; Hussein, Mohamad; Hartley-Brown, Monique A.; Sprung, Robert W.; Perez, Brianna; Liu, Richard Z.; Yoder, Sean; Teer, Jamie; Eschrich, Steven A.; Koomen, John M.

2014-01-01

Purpose Quantitative mass spectrometry assays for immunoglobulins (Igs) are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, e.g. multiple myeloma. Experimental design Using LC-MS/MS data, Ig constant region peptides and transitions were selected for liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM). Quantitative assays were used to assess Igs in serum from 83 patients. Results LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1–4, IgA1–2, IgM, IgD, and IgE, as well as kappa(κ) and lambda(λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 multiple myeloma cell line and two MM patients. Conclusions and Clinical Relevance LC-MRM assays targeting constant region peptides determine the type and isoform of the involved immunoglobulin and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher interassay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques. PMID:24723328

Influence of surgical and minimally invasive facial cosmetic procedures on psychosocial outcomes: a systematic review.

PubMed

Imadojemu, Sotonye; Sarwer, David B; Percec, Ivona; Sonnad, Seema S; Goldsack, Jennifer E; Berman, Morgan; Sobanko, Joseph F

2013-11-01

Millions of surgical and minimally invasive cosmetic procedures of the face are performed each year, but objective clinical measures that evaluate surgical procedures, such as complication rates, have limited utility when applied to cosmetic procedures. While there may be subjective improvements in appearance, it is important to determine if these interventions have an impact on patients in other realms such as psychosocial functioning. This is particularly important in light of the Patient Protection and Affordable Care Act and its emphasis on patient-centered outcomes and effectiveness. To review the literature investigating the impact of facial cosmetic surgery and minimally invasive procedures on relevant psychological variables to guide clinical practice and set norms for clinical performance. English-language randomized clinical trials and prospective cohort studies that preoperatively and postoperatively assessed psychological variables in at least 10 patients seeking surgical or minimally invasive cosmetic procedures of the face. Only 1 study investigating minimally invasive procedures was identified. Most studies reported modest improvement in psychosocial functioning, which included quality of life, self-esteem, and body image. Unfortunately, the overall quality of evidence is limited owing to an absence of control groups, short follow-up periods, or loss to follow-up. The current literature suggests that a number of psychosocial domains may improve following facial cosmetic surgery, although the quality of this evidence is limited (grade of recommendation 2A). Despite the dramatic rise in nonsurgical cosmetic procedures, there is a paucity of information regarding the impact of chemodenervation and soft-tissue augmentation on psychosocial functioning.

High fidelity computational simulation of thrombus formation in Thoratec HeartMate II continuous flow ventricular assist device

PubMed Central

Wu, Wei-Tao; Yang, Fang; Wu, Jingchun; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

2016-01-01

Continuous flow ventricular assist devices (cfVADs) provide a life-saving therapy for severe heart failure. However, in recent years, the incidence of device-related thrombosis (resulting in stroke, device-exchange surgery or premature death) has been increasing dramatically, which has alarmed both the medical community and the FDA. The objective of this study was to gain improved understanding of the initiation and progression of thrombosis in one of the most commonly used cfVADs, the Thoratec HeartMate II. A computational fluid dynamics simulation (CFD) was performed using our recently updated mathematical model of thrombosis. The patterns of deposition predicted by simulation agreed well with clinical observations. Furthermore, thrombus accumulation was found to increase with decreased flow rate, and can be completely suppressed by the application of anticoagulants and/or improvement of surface chemistry. To our knowledge, this is the first simulation to explicitly model the processes of platelet deposition and thrombus growth in a continuous flow blood pump and thereby replicate patterns of deposition observed clinically. The use of this simulation tool over a range of hemodynamic, hematological, and anticoagulation conditions could assist physicians to personalize clinical management to mitigate the risk of thrombosis. It may also contribute to the design of future VADs that are less thrombogenic. PMID:27905492

Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

PubMed

Liao, C-Y; Chien, S-T; Wang, C-C; Chen, I-H; Chiu, H-W; Liu, M-Y; Lin, C-H; Ben, R-J; Tsai, M-K

2015-12-01

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine. © The Author(s) 2015.

Tretinoin for the treatment of photodamaged skin.

PubMed

Ting, William

2010-07-01

Interest in and interventions for photodamaged skin have dramatically increased over the last few years. Although a number of topical therapies have been used for the treatment of photodamaged skin, many therapies remain unproven in efficacy, unapproved, or only supported with limited clinical evidence. Topical retinoids, particularly tretinoin, are the most extensively studied. They have been shown to attenuate and reverse the signs of photodamage, such as coarse wrinkling. In addition, the clinical changes achieved with tretinoin are accompanied by histologic evidence of benefit. The main drawbacks to retinoid use are local irritation and erythema that can limit utility in some patients. New retinoids and formulations specifically optimized to improve cutaneous tolerability have been introduced. Two case reports of patients using low-concentration tretinoin gel 0.05% for the treatment of photodamaged skin are discussed. Over a relatively short treatment period of 4 weeks, tretinoin gel 0.05% was shown to provide both chemoprevention and reversal of photodamage.

The discovery and development of HIV therapy: the new challenges.

PubMed

Perno, Carlo Federico

2011-01-01

The therapy of HIV infection has been dramatically improved over the years, and allowed the achievement of unexpected results. The availability of many drugs, and the knowledge of HIV related pathogenesis, helped in selecting highly effective antiviral therapies, yet today a major challenge stands, that is the selection of the best regimen(s) in clinical practice. In this frame, evidence-based medicine remains a cornerstone of modern medicine, but its structure needs to be adapted to the new challenges, made by an excess of information (not always fully reliable), by highly sophisticated statistical systems that may overlook the clinical practice despite their ability to define the statistical significance, and the limited number of independent controlled studies. The revision of the criteria of evidence-based medicine, and their adaptation to the new tools available, may allow a better contribution to the definition of the best therapy for each single patient.

High-altitude cerebral oedema mimicking stroke.

PubMed

Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

2014-03-26

High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

Rapid amelioration of severe manic episodes with right unilateral ultrabrief pulse ECT: a case series of four patients.

PubMed

Sidorov, Alexey; Mayur, Prashanth

2017-02-01

The aim of this small case series is to describe four cases of severe mania, where ultrabrief pulse electroconvulsive therapy (ECT) was used as a primary mode of treatment. A retrospective file review was undertaken of four patients identified as having received ultrabrief pulse ECT for severe mania. The outcome measures for treatment efficacy were the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI). All the patients showed significant clinical improvement. A comparison of pre- and post-treatment YMRS and CGI scores showed a dramatic decrease in all four cases. However, one patient was shifted to brief pulse ECT due to inadequate response. Ultrabrief pulse ECT may be an effective treatment in cases of severe mania. Due to the very small number of cases in the current case series, no specific conclusions regarding efficacy may be drawn; however, larger, controlled studies would be indicated.

From Genomics to Gene Therapy: Induced Pluripotent Stem Cells Meet Genome Editing.

PubMed

Hotta, Akitsu; Yamanaka, Shinya

2015-01-01

The advent of induced pluripotent stem (iPS) cells has opened up numerous avenues of opportunity for cell therapy, including the initiation in September 2014 of the first human clinical trial to treat dry age-related macular degeneration. In parallel, advances in genome-editing technologies by site-specific nucleases have dramatically improved our ability to edit endogenous genomic sequences at targeted sites of interest. In fact, clinical trials have already begun to implement this technology to control HIV infection. Genome editing in iPS cells is a powerful tool and enables researchers to investigate the intricacies of the human genome in a dish. In the near future, the groundwork laid by such an approach may expand the possibilities of gene therapy for treating congenital disorders. In this review, we summarize the exciting progress being made in the utilization of genomic editing technologies in pluripotent stem cells and discuss remaining challenges toward gene therapy applications.

Vaccines: A review of immune-based interventions to prevent and treat disease.

PubMed

Alemayehu, Demissie; Utt, Eric; Knirsch, Charles

2015-03-01

The enormous gains made in public health during the 20th century, through the prevention and treatment of infectious disease, have contributed to dramatic improvements in the quality and length of the human lifespan. Continued advances in medicine are dependent on addressing several challenges including the increase in existing and new resistance to antibiotics, the decrease in productivity of the research and development (R&D) ecosystem, uncertain regulatory pathways, and an economic environment that rewards innovation for developing therapeutics that involve long cycle times from idea to a product. In this article, we consider important issues pertaining to the development of vaccines with particular emphasis on preclinical requirements, optimal dose selection, design, execution, and reporting of clinical trials for regulatory submission, planning and implementation of post-approval life-cycle programs, and emerging themes in therapeutic vaccines. © 2015, The American College of Clinical Pharmacology.

Maintenance therapy in colon cancer.

PubMed

Giuliani, F; De Vita, F; Colucci, G; Pisconti, S

2010-11-01

In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression". Copyright © 2010 Elsevier Ltd. All rights reserved.

Application of Raman spectroscopy for cervical dysplasia diagnosis

PubMed Central

Kanter, Elizabeth M.; Vargis, Elizabeth; Majumder, Shovan; Keller, Matthew D.; Woeste, Emily; Rao, Gautam G.; Mahadevan-Jansen, Anita

2014-01-01

Cervical cancer is the second most common malignancy among women worldwide, with over 490000 cases diagnosed and 274000 deaths each year. Although current screening methods have dramatically reduced cervical cancer incidence and mortality in developed countries, a “See and Treat” method would be preferred, especially in developing countries. Results from our previous work have suggested that Raman spectroscopy can be used to detect cervical precancers; however, with a classification accuracy of 88%, it was not clinically applicable. In this paper, we describe how incorporating a woman's hormonal status, particularly the point in menstrual cycle and menopausal state, into our previously developed classification algorithm improves the accuracy of our method to 94%. The results of this paper bring Raman spectroscopy one step closer to being utilized in a clinical setting to diagnose cervical dysplasia. Posterior probabilities of class membership, as determined by MRDF-SMLR, for patients regardless of menopausal status, and for pre-menopausal patients only PMID:19343687

A web-based incident reporting system and multidisciplinary collaborative projects for patient safety in a Japanese hospital

PubMed Central

Nakajima, K; Kurata, Y; Takeda, H

2005-01-01



Problem: When patient safety programs were mandated for Japanese health care institutions, a safety culture, a tool for collecting incident reports, an organizational arrangement for multidisciplinary collaboration, and interventional methods for improvement had to be established. Design: Observational study of effects of new patient safety programs. Setting: Osaka University Hospital, a large government-run teaching hospital. Strategy for change: A voluntary and anonymous web-based incident reporting system was introduced. For the new organizational structure a clinical risk management committee, a department of clinical quality management, and area clinical risk managers were established with their respective roles clearly defined to advance the plan-do-study-act cycle and to integrate efforts. For preventive action, alert procedures, staff education, ward rounds by peers, a system oriented approach for reducing errors, and various feedback channels were introduced. Effects of change: Continuous incident reporting by all hospital staff has been observed since the introduction of the new system. Several error inducing situations have been improved: wrong choice of drug in computer prescribing, maladministration of drugs due to a look-alike appearance or confusion about the manipulation of a medical device, and poor after hours service of the blood transfusion unit. Staff participation in educational seminars has been dramatically improved. Ward rounds have detected problematic procedures which needed to be dealt with. Lessons learnt: Patient safety programs based on a web-based incident reporting system, responsible persons, staff education, and a variety of feedback procedures can help promote a safety culture, multidisciplinary collaboration, and strong managerial leadership resulting in system oriented improvement. PMID:15805458

Shear lag sutures: Improved suture repair through the use of adhesives

PubMed Central

Linderman, Stephen W.; Kormpakis, Ioannis; Gelberman, Richard H.; Birman, Victor; Wegst, Ulrike G. K.; Genin, Guy M.; Thomopoulos, Stavros

2015-01-01

Suture materials and surgical knot tying techniques have improved dramatically since their first use over five millennia ago. However, the approach remains limited by the ability of the suture to transfer load to tissue at suture anchor points. Here, we predict that adhesive-coated sutures can improve mechanical load transfer beyond the range of performance of existing suture methods, thereby strengthening repairs and decreasing the risk of failure. The mechanical properties of suitable adhesives were identified using a shear lag model. Examination of the design space for an optimal adhesive demonstrated requirements for strong adhesion and low stiffness to maximize the strength of the adhesive-coated suture repair construct. To experimentally assess the model, we evaluated single strands of sutures coated with highly flexible cyanoacrylates (Loctite 4903 and 4902), cyanoacrylate (Loctite QuickTite Instant Adhesive Gel), rubber cement, rubber/gasket adhesive (1300 Scotch-Weld Neoprene High Performance Rubber & Gasket Adhesive), an albumin-glutaraldehyde adhesive (BioGlue), or poly(dopamine). As a clinically relevant proof-of-concept, cyanoacrylate-coated sutures were then used to perform a clinically relevant flexor digitorum tendon repair in cadaver tissue. The repair performed with adhesive-coated suture had significantly higher strength compared to the standard repair without adhesive. Notably, cyanoacrylate provides strong adhesion with high stiffness and brittle behavior, and is therefore not an ideal adhesive for enhancing suture repair. Nevertheless, the improvement in repair properties in a clinically relevant setting, even using a non-ideal adhesive, demonstrates the potential for the proposed approach to improve outcomes for treatments requiring suture fixation. Further study is necessary to develop a strongly adherent, compliant adhesive within the optimal design space described by the model. PMID:26022966

Negotiating for Change: Modifying Collective Bargaining Agreements for School Turnaround

ERIC Educational Resources Information Center

Weinberg, Rebecca

2011-01-01

Dramatically improving student achievement in a school that has been failing for many years requires dramatically different conditions. Only the most effective teachers and leaders should be in the building, and the leadership must have the flexibility to respond strategically to the needs of the students, with regular input from teachers.…

Fulcrum of Change: Leveraging 50 States to Turn around 5000 Schools

ERIC Educational Resources Information Center

Rhim, Lauren Morando; Redding, Sam

2011-01-01

In 2010, unprecedented levels of resources began to flow through state education agencies (SEAs) to support dramatic change in persistently low-performing schools under the expanded federal School Improvement Grant (SIG) program. The challenge for states is to leverage the federal investment to drive dramatic and sustainable change efforts in…

25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays

PubMed Central

Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li’an; Xia, Liangyu; Qiu, Ling

2015-01-01

Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy. PMID:26420221

25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays.

PubMed

Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li'an; Xia, Liangyu; Qiu, Ling

2015-09-30

Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy.

Guidelines for periodontal care and follow-up during orthodontic treatment in adolescents and young adults

PubMed Central

LEVIN, Liran; EINY, Shmuel; ZIGDON, Hadar; AIZENBUD, Dror; MACHTEI, Eli E.

2012-01-01

Aggressive periodontitis is characterized by non-contributory medical history, rapid attachment loss and bone destruction and familial aggregation of cases. Aggressive periodontitis (both localized and generalized) is usually diagnosed in a young population. This is frequently the age that an orthodontic care is provided to this population. The aim of the present paper is to draw guidelines for periodontal evaluation and monitoring prior to and during active orthodontic treatment. Strict adherence to these guidelines as a routine protocol for periodontal examination prior, during and following orthodontic treatment may dramatically decrease the severity and improve the prognosis of patients with aggressive periodontitis in orthodontic clinics. PMID:23032199

[Secondary hypertension].

PubMed

Yoshida, Yuichi; Shibata, Hirotaka

2015-11-01

Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

Successful treatment of pemphigus vulgaris with etanercept in four patients.

PubMed

Shetty, Anjali; Marcum, Catherine B; Glass, L Frank; Carter, John D

2009-10-01

Pemphigus vulgaris is an autoimmune disease characterized by intraepidermal blister formation. The treatment of pemphigus vulgaris is generally regarded as difficult. Corticosteroids, the drug class of first choice, often must be combined with steroid-sparing agents to prevent hazardous, long-term side effects. The authors describe four patients with severe pemphigus vulgaris who were treated with the tumor necrosis factor (TNF)-alpha antagonist, etanercept, twice weekly. In all four cases, the addition of etanercept produced dramatic clinical improvement and facilitated the reduction of corticosteroids necessary to maintain symptom control. Thus, etanercept may be an effective therapeutic agent for pemphigus vulgaris and should be considered as an alternative treatment option for patients presenting with recalcitrant disease.

A rare case of Weil's disease with alveolar haemorrhage.

PubMed

Chakrabarti, Abhiram; Nandy, Manab; Pal, Dipankar; Mallik, Sudesna

2014-05-01

Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil's disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics.

Art, passion, and neurosurgery: the role of the Society of Neurological Surgeons in academic neurosurgery.

PubMed

Dempsey, Robert J

2011-11-01

Neurosurgery is at a crossroads in a time of economic uncertainty. It is also a time of remarkable potential for innovation resulting in dramatic improvement in the way neurosurgeons care for patients and the quality of outcomes. Analysis of this key time point of neurosurgical history is drawn from reflections for a presidential address to the Society of Neurological Surgeons. It is the author's opinion that the best of academic neurosurgery must and will accept this challenge by developing not only the research but also the creativity and art of what neurosurgeons do for maximal patient benefit in research, educational, and clinical missions. Published by Elsevier Inc.

The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

PubMed Central

Finkelstein, Steven Eric; Timmerman, Robert; McBride, William H.; Schaue, Dörthe; Hoffe, Sarah E.; Mantz, Constantine A.; Wilson, George D.

2011-01-01

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses. PMID:22162711

Dural arteriovenous fistula presenting with exophthalmos and seizures.

PubMed

Feyissa, Anteneh M; Ponce, Lucido L; Patterson, Joel T; Von Ritschl, Rudiger H; Smith, Robert G

2014-03-15

Concomitant seizures and exophthalmos in the context of a temporal dural arteriovenous fistula (dAVF) has not been described before. Here, we report a 55-year-old-male who presented with an 8-month history of progressive painless exophthalmos of his left eye, conjunctival chemosis, reduced vision and new onset complex partial seizures. Cerebral angiography demonstrated Cognard Type IIa left cerebral dAVF fed by branches from the left occipital artery and an accessory meningeal artery, with drainage to the superior ophthalmic vein. Following surgical obliteration of dAVF feeding vessels, our patient had dramatic improvement in visual acuity, proptosis and chemosis along with cessation of clinical seizures. Published by Elsevier B.V.

[Bio-ecological control of chronic liver disease and encephalopathy].

PubMed

Bengmark, S; Di Cocco, P; Clemente, K; Corona, L; Angelico, R; Manzia, T; Famulari, A; Pisani, F; Orlando, G

2011-08-01

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

Basics of particle therapy I: physics

PubMed Central

Park, Seo Hyun

2011-01-01

With the advance of modern radiation therapy technique, radiation dose conformation and dose distribution have improved dramatically. However, the progress does not completely fulfill the goal of cancer treatment such as improved local control or survival. The discordances with the clinical results are from the biophysical nature of photon, which is the main source of radiation therapy in current field, with the lower linear energy transfer to the target. As part of a natural progression, there recently has been a resurgence of interest in particle therapy, specifically using heavy charged particles, because these kinds of radiations serve theoretical advantages in both biological and physical aspects. The Korean government is to set up a heavy charged particle facility in Korea Institute of Radiological & Medical Sciences. This review introduces some of the elementary physics of the various particles for the sake of Korean radiation oncologists' interest. PMID:22984664

Compulsive masturbation in infantile autism treated by mirtazapine.

PubMed

Albertini, Giorgio; Polito, Emilena; Sarà, Marco; Di Gennaro, Giancarlo; Onorati, Paolo

2006-05-01

This case report describes a child with a severe autistic syndrome worsened by hypersexual behavior consisting of compulsive masturbatory activity. Selective serotonin reuptake inhibitors have been reported to be beneficial in reducing hypersexual behaviors. A treatment with mirtazapine improved the entire clinical autistic picture with the disappearance of masturbation. This result suggests that selective serotonin reuptake inhibitors could be useful and promising tools in the treatment of hypersexual behaviors in children with autistic disorders. Moreover, the general, and in some ways unexpected, improvement of the social interaction, communication, and imagination, the dramatic reduction of aloof mannerisms, stereotypes, aggressiveness, and inappropriate emotional response to frustrations, as well as the first appearance of the pragmatic use of language and a strong impetus to emotional development disclosed a new spectrum of possible applications of these drugs, and mirtazapine in particular, suggesting the need for new and more extensive studies on the pharmacotherapy of autism.

Use of moisturizers in dermatologic disease: the role of healthcare providers in optimizing treatment outcomes.

PubMed

Nicol, Noreen Heer

2005-12-01

Although atopic dermatitis is a common cutaneous disorder, patients often are frustrated in their attempts to understand the disease and its treatment. Studies have shown that the patient-provider relationship is key to patient compliance with a skin care regimen and that most patients with atopic dermatitis are eager to be well informed. However, many patients fail to receive an adequate explanation of the causes of atopic dermatitis or to be taught how to apply topical treatments, even though instruction and practical demonstrations are associated with a dramatic improvement in the treatment outcome. Efforts to educate patients regarding the use of moisturizers are correlated with clinical improvement and a reduction in the use of topical medications such as corticosteroids and calcineurin inhibitors. In addition to topical moisturizers, medications, wet wraps, and hydration therapy has become a frequently used practice in the management of atopic dermatitis.

Enhancing Fracture and Wear Resistance of Dentures/Overdentures Utilizing Digital Technology: A Case Series Report.

PubMed

Afify, Ahmed; Haney, Stephan

2016-08-01

Since it was first introduced into the dental world, computer-aided design/computer-aided manufacturing (CAD/CAM) technology has improved dramatically in regards to both data acquisition and fabrication abilities. CAD/CAM is capable of providing well-fitting intra- and extraoral prostheses when sound guidelines are followed. As CAD/CAM technology encompasses both surgical and prosthetic dental applications as well as fixed and removable aspects, it could improve the average quality of dental prostheses compared with the results obtained by conventional manufacturing methods. The purpose of this article is to provide an introduction into the methods in which this technology may be used to enhance the wear and fracture resistance of dentures and overdentures. This article will also showcase two clinical reports in which CAD/CAM technology has been implemented. © 2016 by the American College of Prosthodontists.

The Translational Role of Diffusion Tensor Image Analysis in Animal Models of Developmental Pathologies

PubMed Central

Oguz, Ipek; McMurray, Matthew S.; Styner, Martin; Johns, Josephine M.

2013-01-01

Diffusion Tensor Magnetic Resonance Imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers. PMID:22627095

The Big Glamorous Monster (or Lady Gaga's Adventures at Sea): Improving Student Writing through Dramatic Approaches in Schools

ERIC Educational Resources Information Center

Lee, Bridget Kiger; Enciso, Patricia

2017-01-01

Drawing on assets-oriented, sociocultural theories of imagination and learning, the authors argue that the improvisational qualities and expanded resources of dramatic approaches to teaching make a positive difference in the quality of and persistence in students' story writing. The authors describe findings from a controlled quasi-experimental…

How to Know when Dramatic Change Is on Track: Leading Indicators of School Turnarounds

ERIC Educational Resources Information Center

Kowal, Julie; Ableidinger, Joe

2011-01-01

In recent years, national policymakers have placed new emphasis on "school turnarounds" as a strategy for rapid, dramatic improvement in chronically failing schools, calling on education leaders to turn around performance in the 5,000 lowest-achieving schools nationwide. This goal may seem daunting, given the dismal success rates of…

Listening to a patient: An exploratory experimental investigation into the effects of vocalization and therapist gender on interpreting clinical material.

PubMed

Dauphin, Barry; Halverson, Stacey; Pouliot, Sarah; Slowik, Linda

2018-01-01

Carefully listening to the patient is of paramount importance for psychoanalysis and psychoanalytic psychotherapy. The present study explored whether patient vocalization as well as the gender of the analyst play significant roles in clinical listening. Fifty-one psychoanalysts and psychoanalytic therapists were randomly assigned to listen to one of two dramatized psychoanalytic sessions. The content of the sessions was the same for both versions, but the sessions were dramatized differently. Some differences emerged between the versions, especially on ratings of reality testing, impulse control, pressured speech, patient was confusing, and awareness of imagery. Furthermore, differences emerged between male and female analysts in terms of ratings of intervention strategies and countertransference reactions to the patient material. Session version and gender affect different ratings. Implications of the findings are discussed as is the utility of using more ecologically valid material in conducting empirical research into clinical judgment.

Socio-dramatic affective-relational intervention for adolescents with asperger syndrome & high functioning autism: pilot study.

PubMed

Lerner, Matthew D; Mikami, Amori Yee; Levine, Karen

2011-01-01

This study examined the effectiveness of a novel intervention called 'socio-dramatic affective-relational intervention' (SDARI), intended to improve social skills among adolescents with Asperger syndrome and high functioning autism diagnoses. SDARI adapts dramatic training activities to focus on in vivo practice of areas of social skill deficit among this population. SDARI was administered as a six-week summer program in a community human service agency. Nine SDARI participants and eight age- and diagnosis-group matched adolescents not receiving SDARI were compared on child- and parent-report of social functioning at three week intervals beginning six weeks prior to intervention and ending six weeks post-intervention. Hierarchical Linear Modeling (HLM) was used to estimate growth trends between groups to assess treatment outcomes and post-treatment maintenance. Results indicated significant improvement and post-treatment maintenance among SDARI participants on several measures of child social functioning. Implications for practice and research are discussed.

Clinical simulation training improves the clinical performance of Chinese medical students

PubMed Central

Zhang, Ming-ya; Cheng, Xin; Xu, An-ding; Luo, Liang-ping; Yang, Xuesong

2015-01-01

Background Modern medical education promotes medical students’ clinical operating capacity rather than the mastery of theoretical knowledge. To accomplish this objective, clinical skill training using various simulations was introduced into medical education to cultivate creativity and develop the practical ability of students. However, quantitative analysis of the efficiency of clinical skill training with simulations is lacking. Methods In the present study, we compared the mean scores of medical students (Jinan University) who graduated in 2013 and 2014 on 16 stations between traditional training (control) and simulative training groups. In addition, in a clinical skill competition, the objective structured clinical examination (OSCE) scores of participating medical students trained using traditional and simulative training were compared. The data were statistically analyzed and qualitatively described. Results The results revealed that simulative training could significantly enhance the graduate score of medical students compared with the control. The OSCE scores of participating medical students in the clinical skill competition, trained using simulations, were dramatically higher than those of students trained through traditional methods, and we also observed that the OSCE marks were significantly increased for the same participant after simulative training for the clinical skill competition. Conclusions Taken together, these data indicate that clinical skill training with a variety of simulations could substantially promote the clinical performance of medical students and optimize the resources used for medical education, although a precise analysis of each specialization is needed in the future. PMID:26478142

Quantification of peptides from immunoglobulin constant and variable regions by LC-MRM MS for assessment of multiple myeloma patients.

PubMed

Remily-Wood, Elizabeth R; Benson, Kaaron; Baz, Rachid C; Chen, Y Ann; Hussein, Mohamad; Hartley-Brown, Monique A; Sprung, Robert W; Perez, Brianna; Liu, Richard Z; Yoder, Sean J; Teer, Jamie K; Eschrich, Steven A; Koomen, John M

2014-10-01

Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM). Using LC-MS/MS data, Ig constant region peptides, and transitions were selected for LC-MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide-based LC-MRM are used to define peptides for quantification of the disease-specific Ig. LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1-4, IgA1-2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients. LC-MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter-assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Imaging and Analytics: The changing face of Medical Imaging

NASA Astrophysics Data System (ADS)

Foo, Thomas

There have been significant technological advances in imaging capability over the past 40 years. Medical imaging capabilities have developed rapidly, along with technology development in computational processing speed and miniaturization. Moving to all-digital, the number of images that are acquired in a routine clinical examination has increased dramatically from under 50 images in the early days of CT and MRI to more than 500-1000 images today. The staggering number of images that are routinely acquired poses significant challenges for clinicians to interpret the data and to correctly identify the clinical problem. Although the time provided to render a clinical finding has not substantially changed, the amount of data available for interpretation has grown exponentially. In addition, the image quality (spatial resolution) and information content (physiologically-dependent image contrast) has also increased significantly with advances in medical imaging technology. On its current trajectory, medical imaging in the traditional sense is unsustainable. To assist in filtering and extracting the most relevant data elements from medical imaging, image analytics will have a much larger role. Automated image segmentation, generation of parametric image maps, and clinical decision support tools will be needed and developed apace to allow the clinician to manage, extract and utilize only the information that will help improve diagnostic accuracy and sensitivity. As medical imaging devices continue to improve in spatial resolution, functional and anatomical information content, image/data analytics will be more ubiquitous and integral to medical imaging capability.

Laser speckle and skin cancer: skin roughness assessment

NASA Astrophysics Data System (ADS)

Lee, Tim K.; Tchvialeva, Lioudmila; Zeng, Haishan; McLean, David I.; Lui, Harvey

2009-10-01

Incidence of skin cancer has been increasing rapidly since the last few decades. Non-invasive optical diagnostic tools may improve the diagnostic accuracy. In this paper, skin structure, skin cancer statistics and subtypes of skin cancer are briefly reviewed. Among the subtypes, malignant melanoma is the most aggressive and dangerous; early detection dramatically improves the prognosis. Therefore, a non-invasive diagnostic tool for malignant melanoma is especially needed. In addition, in order for the diagnostic tool to be useful, it must be able to differentiate melanoma from common skin conditions such as seborrheic keratosis, a benign skin disease that resembles melanoma according to the well known clinical-assessment ABCD rule. The key diagnostic feature between these two diseases is surface roughness. Based on laser speckle contrast, our research team has recently developed a portable, optical, non-invasive, in-vivo diagnostic device for quantifying skin surface roughness. The methodology of our technique is described in details. Examining the preliminary data collected in a pilot clinical study for the prototype, we found that there was a difference in roughness between melanoma and seborrheic keratosis. In fact, there was a perfect cutoff value for the two diseases based on our initial data.

Towards Prevention of Breast Cancer: What Are the Clinical Challenges?

PubMed

Borgquist, Signe; Hall, Per; Lipkus, Isaac; Garber, Judy E

2018-05-01

The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. There are several barriers to overcome before prevention becomes an established part of breast cancer management. The objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering the aspects relevant for a breast cancer prevention trial. Herein, the following five areas are discussed: (i) Adequate tools for identification of women at high risk of breast cancer suggestively entitled Prevent! Online. (ii) Consensus on the definition of high risk, which is regarded as mandatory for all risk communication and potential prophylactic interventions. (iii) Risk perception and communication regarding risk information. (iv) Potential ethical concerns relevant for future breast cancer prevention programs. (v) Risk-reducing programs involving multileveled prevention depending on identified risk. Taken together, devoted efforts from both policy makers and health care providers are warranted to improve risk assessment and risk counseling in women at risk for breast cancer to optimize the prevention of breast cancer. Cancer Prev Res; 11(5); 255-64. ©2018 AACR . ©2018 American Association for Cancer Research.

Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker.

PubMed

Ronald, John A; Chuang, Hui-Yen; Dragulescu-Andrasi, Anca; Hori, Sharon S; Gambhir, Sanjiv S

2015-03-10

Earlier detection of cancers can dramatically improve the efficacy of available treatment strategies. However, despite decades of effort on blood-based biomarker cancer detection, many promising endogenous biomarkers have failed clinically because of intractable problems such as highly variable background expression from nonmalignant tissues and tumor heterogeneity. In this work we present a tumor-detection strategy based on systemic administration of tumor-activatable minicircles that use the pan-tumor-specific Survivin promoter to drive expression of a secretable reporter that is detectable in the blood nearly exclusively in tumor-bearing subjects. After systemic administration we demonstrate a robust ability to differentiate mice bearing human melanoma metastases from tumor-free subjects for up to 2 wk simply by measuring blood reporter levels. Cumulative change in reporter levels also identified tumor-bearing subjects, and a receiver operator-characteristic curve analysis highlighted this test's performance with an area of 0.918 ± 0.084. Lung tumor burden additionally correlated (r(2) = 0.714; P < 0.05) with cumulative reporter levels, indicating that determination of disease extent was possible. Continued development of our system could improve tumor detectability dramatically because of the temporally controlled, high reporter expression in tumors and nearly zero background from healthy tissues. Our strategy's highly modular nature also allows it to be iteratively optimized over time to improve the test's sensitivity and specificity. We envision this system could be used first in patients at high risk for tumor recurrence, followed by screening high-risk populations before tumor diagnosis, and, if proven safe and effective, eventually may have potential as a powerful cancer-screening tool for the general population.

Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection.

PubMed

El Kassas, Mohamed; Elbaz, Tamer; Hafez, Enas; Wifi, Mohamed Naguib; Esmat, Gamal

2017-06-01

Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families. Areas covered: In this review, the authors summarize data from of one of the recently developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333. Herein, the authors discuss the drug discovery data for dasabuvir including data from preclinical, toxicological resistance studies. The authors also review dasabuvir's clinical efficacy across various clinical challenges, in addition to its limitations in clinical practice. Expert opinion: Dasabuvir represents an important medical advance when used as a combination therapy for HCV. Unfortunately, it does present limitations like low genotypic coverage and further research is still required to address some of the lingering issues.

Simulation study of the second-generation MR-compatible SPECT system based on the inverted compound-eye gamma camera design

NASA Astrophysics Data System (ADS)

Lai, Xiaochun; Meng, Ling-Jian

2018-02-01

In this paper, we present simulation studies for the second-generation MRI compatible SPECT system, MRC-SPECT-II, based on an inverted compound eye (ICE) gamma camera concept. The MRC-SPECT-II system consists of a total of 1536 independent micro-pinhole-camera-elements (MCEs) distributed in a ring with an inner diameter of 6 cm. This system provides a FOV of 1 cm diameter and a peak geometrical efficiency of approximately 1.3% (the typical levels of 0.1%-0.01% found in modern pre-clinical SPECT instrumentations), while maintaining a sub-500 μm spatial resolution. Compared to the first-generation MRC-SPECT system (MRC-SPECT-I) (Cai 2014 Nucl. Instrum. Methods Phys. Res. A 734 147-51) developed in our lab, the MRC-SPECT-II system offers a similar resolution with dramatically improved sensitivity and greatly reduced physical dimension. The latter should allow the system to be placed inside most clinical and pre-clinical MRI scanners for high-performance simultaneous MRI and SPECT imaging.

Acute clinical recovery from sport-related concussion.

PubMed

Nelson, Lindsay D; Janecek, Julie K; McCrea, Michael A

2013-12-01

Concussion is a highly prevalent injury in contact and collision sports that has historically been poorly understood. An influx of sport-concussion research in recent years has led to a dramatic improvement in our understanding of the injury's defining characteristics and natural history of recovery. In this review, we discuss the current state of knowledge regarding the characteristic features of concussion and typical acute course of recovery, with an emphasis on the aspects of functioning most commonly assessed by clinicians and researchers (e.g., symptoms, cognitive deficits, postural stability). While prototypical clinical recovery is becoming better understood, questions remain regarding what factors (e.g., injury severity, demographic variables, history of prior concussions, psychological factors) may explain individual variability in recovery. Although research concerning individual differences in response to concussion is relatively new, and in many cases limited methodologically, we discuss the evidence about several potential moderators of concussion recovery and point out areas for future research. Finally, we describe how increased knowledge about the negative effects of and recovery following concussion has been translated into clinical guidelines for managing concussed athletes.

Ultrasound enhanced thrombolysis: Clinical evidence

NASA Astrophysics Data System (ADS)

Alexandrov, Andrei V.

2005-04-01

Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

A Rural School/Community: A Case Study of a Dramatic Turnaround & Its Implications for School Improvement.

ERIC Educational Resources Information Center

Carlson, Robert V.

This paper presents a case study of a rural community exhibiting a dramatic turnaround in community support for a new school bond issue. Demographic change was partly responsible for the change in community attitudes, with two waves of immigration altering the long-term conservative orientation of this community. After a series of failed…

Current and Emerging Therapies for Lupus Nephritis

PubMed Central

Parikh, Samir V.

2016-01-01

The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments. PMID:27283496

Herpes simplex virus type 2-associated recurrent aseptic (Mollaret's) meningitis in genitourinary medicine clinic: a case report.

PubMed

Abou-Foul, Ahmad K; Buhary, Thajunisha M; Gayed, Sedki L

2014-01-01

Cases of idiopathic recurrent benign aseptic meningitis were first described by Mollaret. Today, herpes simplex virus (HSV) is considered the cause of most cases of Mollaret's meningitis. A 40-year-old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions. He had HSV-2-positive genital ulcers 8 years earlier. One year after the first infection, he developed severe recurrent attacks of headache associated with meningitis symptoms. The results of all radiological and biochemical tests were normal, but the patient reported a correlation between his attacks and genital herpes flare-ups. We diagnosed the patient with Mollaret's meningitis and started him on continuous suppressive acyclovir therapy, which resulted in marked clinical improvement. Mollaret's meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset, short duration, and spontaneous remission with unpredictable recurrence. We believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis, prior to which, affected patients usually have many unnecessary investigations and treatments. Therefore, detailed sexual history should be sought in all patients with aseptic meningitis, and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions. Continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle.

Bronchopulmonary dysplasia: clinical practices in five Portuguese neonatal intensive care units.

PubMed

Guimarães, H; Rocha, G; Vasconcellos, G; Proença, E; Carreira, M L; Sossai, M R; Morais, B; Martins, I; Rodrigues, T; Severo, M

2010-01-01

With the advent of surfactant, prenatal corticosteroids (PNC) and advances in technology, the survival rate of extremely low birth weight (ELBW) infants has improved dramatically. Rates of bronchopulmonary dysplasia (BPD) vary widely among neonatal intensive care units (NICUs) and many studies using multiple interventions have shown some improvement in BPD rates. Implementing potentially better practices to reduce BPD has been an effort made over the last few decades. To compare five Portuguese NICUs in terms of clinical practices in very low birth weight (VLBW) infants, in order to develop better practices to prevent BPD. 256 preterm neonates, gestational age (GA) <30 weeks and/or birthweight (BW) <1250g admitted to five Portuguese NICUs (centers 1 to 5) between 1st January 2004 and 31st December 2006, were studied. VLBW infants with major malformations, grade IV intraventricular haemorrhage in the first week of life and metabolic or neuromuscular disease were excluded. BPD was defined as oxygen dependency at 36 weeks of postconceptional age. We considered a practice to be improved as clinically significant whenever a decrease greater than 10% in the prevalence of BPD adjusted for the practice, GA and BW was achieved compared to BPD prevalence adjusted only for GA and BW. The overall prevalence of BPD was 12.9%. Our results revealed that PNC use should be improved in centers 4 and 5; fluid policy in center 4; oxygen therapy and sepsis prevention in centers 1 and 2. Patent ductus arteriosus (PDA) treatment should be improved in center 2. The implementation of potentially better practices to reduce lung injury in neonates in Portuguese NICUs, according to each NICU, must be addressed to increase the prescription of PNC, to use a lower FiO2, to be careful with fluid administration in the first weeks of life and to prevent PDA and sepsis. It is necessary to follow guidelines, recommendations or protocols to improve quality in the prevention of BPD.

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

[Symptoms of Celiac disease in childhood].

PubMed

Mouterde, O; Dumant, C; Mallet, E

2013-06-01

The knowledge regarding celiac disease has increased dramatically in recent years, due to the availability of accurate serologic markers. Mass screening studies have shown that the prevalence of sensitization can be as high as 1/80. The range of symptoms is wide, from the classic growth failure, denutrition and diarrhea in infancy to clinically and histologically asymptomatic sensitized subjects. The interest of a routine mass screening is debated. The classical celiac disease in infancy is well known. Atypical symptoms and potentially associated disease are more frequent and potentially confounding. Physicians should be aware of any clue for celiac disease in atypical cases in order to improve the diagnostic yield, and therefore avoiding short or long term consequences. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Genomics and epigenomics of clear cell renal cell carcinoma: recent developments and potential applications.

PubMed

Rydzanicz, Małgorzata; Wrzesiński, Tomasz; Bluyssen, Hans A R; Wesoły, Joanna

2013-12-01

Majority of clear cell renal cell carcinomas (ccRCCs) are diagnosed in the advanced metastatic stage resulting in dramatic decrease of patient survival. Thereby, early detection and monitoring of the disease may improve prognosis and treatment results. Recent technological advances enable the identification of genetic events associated with ccRCC and reveal significant molecular heterogeneity of ccRCC tumors. This review summarizes recent findings in ccRCC genomics and epigenomics derived from chromosomal aberrations, DNA sequencing and methylation, mRNA, miRNA expression profiling experiments. We provide a molecular insight into ccRCC pathology and recapitulate possible clinical applications of genomic alterations as predictive and prognostic biomarkers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

VGKC positive autoimmune encephalopathy mimicking dementia.

PubMed

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O' Toole, Orna

2011-12-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan's syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment.

A Plant-Based Nutrition Program.

PubMed

Evans, Joanne; Magee, Alexandra; Dickman, Kathy; Sutter, Rebecca; Sutter, Caroline

2017-03-01

: Proper nutrition is an important but often overlooked component of preventive care and disease management. Following a plant-based diet in particular has been shown to have dramatic effects on health and well-being in a relatively short period of time. For this reason, nurses at three faculty-led community health clinics participated in a nutrition educational program, following a plant-based diet for 21 days. They sought to improve their knowledge of plant-based nutrition and experience firsthand the benefits of such a diet. The authors conclude that this type of program, with its experiential component and beneficial personal health results, has the potential to influence a larger nursing audience as participants apply their knowledge and experience to patient care and to classroom discussions with nursing students.

Exacerbation of experimental autoimmune encephalomyelitis by passive transfer of IgG antibodies from a multiple sclerosis patient responsive to immunoadsorption.

PubMed

Pedotti, Rosetta; Musio, Silvia; Scabeni, Stefano; Farina, Cinthia; Poliani, Pietro Luigi; Colombo, Emanuela; Costanza, Massimo; Berzi, Angela; Castellucci, Fabrizio; Ciusani, Emilio; Confalonieri, Paolo; Hemmer, Bernhard; Mantegazza, Renato; Antozzi, Carlo

2013-09-15

The pathogenic role of antibodies in multiple sclerosis (MS) is still controversial. We transferred to mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, IgG antibodies purified from a MS patient presenting a dramatic clinical improvement during relapse after selective IgG removal with immunoadsorption. Passive transfer of patient's IgG exacerbated motor paralysis and increased mouse central nervous system (CNS) inflammation and demyelination. Binding of patient's IgG was demonstrated in mouse CNS, with a diffuse staining of white matter oligodendrocytes. These data support a growing body of evidence that antibodies can play an important role in the pathobiology of MS. Copyright © 2013 Elsevier B.V. All rights reserved.

IL-7 Promotes T Cell Viability, Trafficking, and Functionality and Improves Survival in Sepsis

PubMed Central

Unsinger, Jacqueline; McGlynn, Margaret; Kasten, Kevin R.; Hoekzema, Andrew S.; Watanabe, Eizo; Muenzer, Jared T.; McDonough, Jacquelyn S.; Tschoep, Johannes; Ferguson, Thomas A.; McDunn, Jonathan E.; Morre, Michel; Hildeman, David A.; Caldwell, Charles C.; Hotchkiss, Richard S.

2010-01-01

Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T cells, restored IFN-γ production, and improved immune effector cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-γ– and T cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis. PMID:20200277

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

[Pharmacotherapy of solid tumors. New hopes and frustrations].

PubMed

Grünwald, V; Rickmann, M

2014-10-01

Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

PubMed

Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

2018-04-24

Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.

The use of Electrolyte Additives to Improve the High Temperature Resilience of Li-Ion Cells

NASA Technical Reports Server (NTRS)

Smart, Marshall C.; Lucht, B. L.; Ratnakumar, Bugga V.

2007-01-01

This viewgraph presentation reviews the use of electrolyte additves to improve the resillience of Lithium ion cells. The objective of this work is to identify lithium-ion electrolytes, which will lead to Li-ion cells with a wide operational temperature range (+60 to -60 C), and to develop Li-ion electrolytes which result in cells that display improved high temperature resilience. Significant improvement in the high temperature resilience of Li-ion cells containing these additives was observed, with the most dramatic benefit being displayed by addition of DMAc. When the electrochemical properties of the individual electrodes were analyzed, the degradation of the anode kinetics was slowed most dramatically by the incorporation of DMAc into the electrolytes. Whereas, the greatest retention in the cathode kinetics was observed in the cell containing the electrolyte with VC added.

Brief educational interventions to improve performance on novel quality metrics in ambulatory settings in Kenya: A multi-site pre-post effectiveness trial.

PubMed

Korom, Robert Ryan; Onguka, Stephanie; Halestrap, Peter; McAlhaney, Maureen; Adam, Mary

2017-01-01

The quality of primary care delivered in resource-limited settings is low. While some progress has been made using educational interventions, it is not yet clear how to sustainably improve care for common acute illnesses in the outpatient setting. Management of urinary tract infection is particularly important in resource-limited settings, where it is commonly diagnosed and associated with high levels of antimicrobial resistance. We describe an educational programme targeting non-physician health care providers and its effects on various clinical quality metrics for urinary tract infection. We used a series of educational interventions including 1) formal introduction of a clinical practice guideline, 2) peer-to-peer chart review, and 3) peer-reviewed literature describing local antimicrobial resistance patterns. Interventions were conducted for clinical officers (N = 24) at two outpatient centers near Nairobi, Kenya over a one-year period. The medical records of 474 patients with urinary tract infections were scored on five clinical quality metrics, with the primary outcome being the proportion of cases in which the guideline-recommended antibiotic was prescribed. The results at baseline and following each intervention were compared using chi-squared tests and unpaired two-tailed T-tests for significance. Logistic regression analysis was used to assess for possible confounders. Clinician adherence to the guideline-recommended antibiotic improved significantly during the study period, from 19% at baseline to 68% following all interventions (Χ2 = 150.7, p < 0.001). The secondary outcome of composite quality score also improved significantly from an average of 2.16 to 3.00 on a five-point scale (t = 6.58, p < 0.001). Interventions had different effects at different clinical sites; the primary outcome of appropriate antibiotic prescription was met 83% of the time at Penda Health, and 50% of the time at AICKH, possibly reflecting differences in onboarding and management of clinical officers. Logistic regression analysis showed that intervention stage and clinical site were independent predictors of the primary outcome (p < 0.0001), while all other features, including provider and patient age, were not significant at a conservative threshold of p < 0.05. This study shows that brief educational interventions can dramatically improve the quality of care for routine acute illnesses in the outpatient setting. Measurement of quality metrics allows for further targeting of educational interventions depending on the needs of the providers and the community. Further study is needed to expand routine measurement of quality metrics and to identify the interventions that are most effective in improving quality of care.

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.

PubMed

Freitas, J; Santos, R; Azevedo, E; Costa, O; Carvalho, M; de Freitas, A F

2000-10-01

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.

Asymptomatic myotonia congenita unmasked by severe hypothyroidism.

PubMed

Passeri, Elena; Sansone, Valeria A; Verdelli, Chiara; Mendola, Marco; Corbetta, Sabrina

2014-04-01

Myotonia congenita is an inherited muscle disorder sustained by mutations in the skeletal muscle chloride channel gene CLCN1. Symptoms vary from mild to severe and generalized myotonia and worsen with cold, stressful events and hormonal fluctuations. Here we report the case of a young woman who sought medical attention because of subacute onset of diffuse and severe limb myotonia. CLCN1 gene sequencing showed a heterozygous transversion (T550M), two polymorphisms and one silent mutation. Thyroid function screening revealed severe hypothyroidism. She was placed on l-thyroxine replacement therapy which dramatically improved myotonia. We conclude that hypothyroidism unmasked a genetically determined, clinically asymptomatic chloride channelopathy. Diagnostic work-up in patients with clinically isolated myotonia should not be limited to genetic screening of non-dystrophic or dystrophic myotonias. Considering the high prevalence of hypothyroidism in females, systematic thyroid function screening by looking for additional hypothyroid symptoms and serum TSH levels measurement is mandatory in these patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Dendritic cell-based vaccines for pancreatic cancer and melanoma.

PubMed

Mulé, James J

2009-09-01

Based on leads from our recent animal studies, we are embarking on a series of new clinical trials to evaluate potential improvements in dendritic cell (DC)-based vaccines for melanoma and pancreatic cancer. The first new strategy involves the use of a powerful chemokine (denoted secondary lymphoid tissue chemokine; SLC/CCL-21), which can both create functioning lymph node-like structures at sites of vaccination with tumor-loaded DCs and dramatically enhance vaccine efficacy in animal tumor models. Using this strategy, we are embarking on a clinical trial in melanoma patients with the intent to create functioning, ectopic, lymph node-like structures to enhance host antitumor immunity. The second strategy, in the setting of pancreatic cancer, involves a gene therapy and immunotherapy combination of a locally administered tumor necrosis factor-alpha gene vector followed by radiation (to induce tumor apoptosis/necrosis) and intratumorally administered monocyte-derived DCs (to uptake and present antigens from dying tumor cells to elicit potent, systemic, antitumor immunity).

Facial Transplantation Surgery Introduction

PubMed Central

2015-01-01

Severely disfiguring facial injuries can have a devastating impact on the patient's quality of life. During the past decade, vascularized facial allotransplantation has progressed from an experimental possibility to a clinical reality in the fields of disease, trauma, and congenital malformations. This technique may now be considered a viable option for repairing complex craniofacial defects for which the results of autologous reconstruction remain suboptimal. Vascularized facial allotransplantation permits optimal anatomical reconstruction and provides desired functional, esthetic, and psychosocial benefits that are far superior to those achieved with conventional methods. Along with dramatic improvements in their functional statuses, patients regain the ability to make facial expressions such as smiling and to perform various functions such as smelling, eating, drinking, and speaking. The ideas in the 1997 movie "Face/Off" have now been realized in the clinical field. The objective of this article is to introduce this new surgical field, provide a basis for examining the status of the field of face transplantation, and stimulate and enhance facial transplantation studies in Korea. PMID:26028914

Facial transplantation surgery introduction.

PubMed

Eun, Seok-Chan

2015-06-01

Severely disfiguring facial injuries can have a devastating impact on the patient's quality of life. During the past decade, vascularized facial allotransplantation has progressed from an experimental possibility to a clinical reality in the fields of disease, trauma, and congenital malformations. This technique may now be considered a viable option for repairing complex craniofacial defects for which the results of autologous reconstruction remain suboptimal. Vascularized facial allotransplantation permits optimal anatomical reconstruction and provides desired functional, esthetic, and psychosocial benefits that are far superior to those achieved with conventional methods. Along with dramatic improvements in their functional statuses, patients regain the ability to make facial expressions such as smiling and to perform various functions such as smelling, eating, drinking, and speaking. The ideas in the 1997 movie "Face/Off" have now been realized in the clinical field. The objective of this article is to introduce this new surgical field, provide a basis for examining the status of the field of face transplantation, and stimulate and enhance facial transplantation studies in Korea.

The Genomic Landscape of Balanced Cytogenetic Abnormalities Associated with Human Congenital Anomalies

PubMed Central

Redin, Claire; Brand, Harrison; Collins, Ryan L.; Kammin, Tammy; Mitchell, Elyse; Hodge, Jennelle C.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Abbott, Mary-Alice; Abdul-Rahman, Omar A.; Aberg, Erika; Adley, Rhett; Alcaraz-Estrada, Sofia L.; Alkuraya, Fowzan S.; An, Yu; Anderson, Mary-Anne; Antolik, Caroline; Anyane-Yeboa, Kwame; Atkin, Joan F.; Bartell, Tina; Bernstein, Jonathan A.; Beyer, Elizabeth; Blumenthal, Ian; Bongers, Ernie M.H.F.; Brilstra, Eva H.; Brown, Chester W.; Brüggenwirth, Hennie T.; Callewaert, Bert; Chiang, Colby; Corning, Ken; Cox, Helen; Cuppen, Edwin; Currall, Benjamin B.; Cushing, Tom; David, Dezso; Deardorff, Matthew A.; Dheedene, Annelies; D’Hooghe, Marc; de Vries, Bert B.A.; Earl, Dawn L.; Ferguson, Heather L.; Fisher, Heather; FitzPatrick, David R.; Gerrol, Pamela; Giachino, Daniela; Glessner, Joseph T.; Gliem, Troy; Grady, Margo; Graham, Brett H.; Griffis, Cristin; Gripp, Karen W.; Gropman, Andrea L.; Hanson-Kahn, Andrea; Harris, David J.; Hayden, Mark A.; Hill, Rosamund; Hochstenbach, Ron; Hoffman, Jodi D.; Hopkin, Robert J.; Hubshman, Monika W.; Innes, A. Micheil; Irons, Mira; Irving, Melita; Jacobsen, Jessie C.; Janssens, Sandra; Jewett, Tamison; Johnson, John P.; Jongmans, Marjolijn C.; Kahler, Stephen G.; Koolen, David A.; Korzelius, Jerome; Kroisel, Peter M.; Lacassie, Yves; Lawless, William; Lemyre, Emmanuelle; Leppig, Kathleen; Levin, Alex V.; Li, Haibo; Li, Hong; Liao, Eric C.; Lim, Cynthia; Lose, Edward J.; Lucente, Diane; Macera, Michael J.; Manavalan, Poornima; Mandrile, Giorgia; Marcelis, Carlo L.; Margolin, Lauren; Mason, Tamara; Masser-Frye, Diane; McClellan, Michael W.; Zepeda Mendoza, Cinthya J.; Menten, Björn; Middelkamp, Sjors; Mikami, Liya R.; Moe, Emily; Mohammed, Shehla; Mononen, Tarja; Mortenson, Megan E.; Moya, Graciela; Nieuwint, Aggie W.; Ordulu, Zehra; Parkash, Sandhya; Pauker, Susan P.; Pereira, Shahrin; Perrin, Danielle; Phelan, Katy; Piña Aguilar, Raul E.; Poddighe, Pino J.; Pregno, Giulia; Raskin, Salmo; Reis, Linda; Rhead, William; Rita, Debra; Renkens, Ivo; Roelens, Filip; Ruliera, Jayla; Rump, Patrick; Schilit, Samantha L.P.; Shaheen, Ranad; Sparkes, Rebecca; Spiegel, Erica; Stevens, Blair; Stone, Matthew R.; Tagoe, Julia; Thakuria, Joseph V.; van Bon, Bregje W.; van de Kamp, Jiddeke; van Der Burgt, Ineke; van Essen, Ton; van Ravenswaaij-Arts, Conny M.; van Roosmalen, Markus J.; Vergult, Sarah; Volker-Touw, Catharina M.L.; Warburton, Dorothy P.; Waterman, Matthew J.; Wiley, Susan; Wilson, Anna; Yerena-de Vega, Maria de la Concepcion A.; Zori, Roberto T.; Levy, Brynn; Brunner, Han G.; de Leeuw, Nicole; Kloosterman, Wigard P.; Thorland, Erik C.; Morton, Cynthia C.; Gusella, James F.; Talkowski, Michael E.

2017-01-01

Despite their clinical significance, characterization of balanced chromosomal abnormalities (BCAs) has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and revealed complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. This study proposes that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements, and provides insight into novel pathogenic mechanisms such as altered regulation due to changes in chromosome topology. PMID:27841880

Multifunction Sr, Co and F co-doped microporous coating on titanium of antibacterial, angiogenic and osteogenic activities

PubMed Central

Zhou, Jianhong; Zhao, Lingzhou

2016-01-01

Advanced multifunction titanium (Ti) based bone implant with antibacterial, angiogenic and osteogenic activities is stringently needed in clinic, which may be accomplished via incorporation of proper inorganic bioactive elements. In this work, microporous TiO2/calcium-phosphate coating on Ti doped with strontium, cobalt and fluorine (SCF-TiCP) was developed, which had a hierarchical micro/nano-structure with a microporous structure evenly covered with nano-grains. SCF-TiCP greatly inhibited the colonization and growth of both gram-positive and gram-negative bacteria. No cytotoxicity appeared for SCF-TiCP. Furthermore, SCF-TiCP stimulated the expression of key angiogenic factors in rat bone marrow stem cells (MSCs) and dramatically enhanced MSC osteogenic differentiation. The in vivo animal test displayed that SCF-TiCP induced more new bone and tighter implant/bone bonding. In conclusion, multifunction SCF-TiCP of antibacterial, angiogenic and osteogenic activities is a promising orthopedic and dental Ti implant coating for improved clinical performance. PMID:27353337

Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations.

PubMed

Adams, Christopher F; Rai, Ahmad; Sneddon, Gregor; Yiu, Humphrey H P; Polyak, Boris; Chari, Divya M

2015-01-01

Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, 'magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥90%) of primary neural stem cells (NSCs)-a 'hard-to-label' transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapid-fire improvement with short-cycle kaizen.

PubMed

Heard, E

1999-05-01

Continuous improvement is an attractive idea, but it is typically more myth than reality. SCK is no myth. It delivers dramatic improvements in traditional measures quickly. SCK accomplishes this via kaizens: rapid, repeated, time-compressed changes for the better in bite-sized chunks of the business.

WE-DE-201-01: BEST IN PHYSICS (THERAPY): A Fast Multi-Target Inverse Treatment Planning Strategy Optimizing Dosimetric Measures for High-Dose-Rate (HDR) Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guthier, C; University Medical Center Mannheim, Mannheim; Harvard Medical School, Boston, MA

Purpose: Inverse treatment planning (ITP) for interstitial HDR brachytherapy of gynecologic cancers seeks to maximize coverage of the clinical target volumes (tumor and vagina) while respecting dose-volume-histogram related dosimetric measures (DMs) for organs at risk (OARs). Commercially available ITP tools do not support DM-based planning because it is computationally too expensive to solve. In this study we present a novel approach that allows fast ITP for gynecologic cancers based on DMs for the first time. Methods: This novel strategy is an optimization model based on a smooth DM-based objective function. The smooth approximation is achieved by utilizing a logistic functionmore » for the evaluation of DMs. The resulting nonconvex and constrained optimization problem is then optimized with a BFGS algorithm. The model was evaluated using the implant geometry extracted from 20 patient treatment plans under an IRB-approved retrospective study. For each plan, the final DMs were evaluated and compared to the original clinical plans. The CTVs were the contoured tumor volume and the contoured surface of the vagina. Statistical significance was evaluated with a one-sided paired Wilcoxon signed-rank test. Results: As did the clinical plans, all generated plans fulfilled the defined DMs for OARs. The proposed strategy showed a statistically significant improvement (p<0.001) in coverage of the tumor and vagina, with absolute improvements of related DMs of (6.9 +/− 7.9)% and (28.2 +/− 12.0)%, respectively. This was achieved with a statistically significant (p<0.01) decrease of the high-dose-related DM for the tumor. The runtime of the optimization was (2.3 +/− 2.0) seconds. Conclusion: We demonstrated using clinical data that our novel approach allows rapid DM-based optimization with improved coverage of CTVs with fewer hot spots. Being up to three orders of magnitude faster than the current clinical practice, the method dramatically shortens planning time.« less

A review of dengue fever: a resurging tropical disease.

PubMed

Mangold, Karen A; Reynolds, Sally L

2013-05-01

Dengue is a resurging mosquito-borne disease that is often contracted in U.S. travelers to Latin America, Asia, and the Caribbean. The clinical symptoms range from a simple febrile illness to hemorrhagic fever or shock. The clinical course has a wide range of outcomes, and adequate supportive care can reduce mortality rates dramatically. Repeated exposures to the virus can lead to a more complicated clinical course.

Inadequate management of pregnancy-associated listeriosis: lessons from four case reports.

PubMed

Charlier, C; Goffinet, F; Azria, E; Leclercq, A; Lecuit, M

2014-03-01

Listeria monocytogenes infection during pregnancy can lead to dramatic fetal or neonatal outcomes. No clinical trial has evaluated treatment options, and retrospective studies of cases are therefore important to define optimal regimens. We report four cases of materno-neonatal listeriosis illustrating inadequate antimicrobial therapy management and discuss recommended treatment options. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Clinical pharmacy travel medicine services: a new frontier.

PubMed

Jackson, Adam B; Humphries, Tammy L; Nelson, Kent M; Helling, Dennis K

2004-12-01

Travel to remote destinations has increased dramatically in recent years. The Clinical Pharmacy International Travel Clinic (CPITC) was established in 1991 in the Kaiser Permanente Colorado Region to provide pre-travel advice to members to decrease their risk of travel-related diseases. The CPITC is unique from other travel medicine clinics because it is a pharmacist-run telepharmacy service. The team includes an infectious diseases physician, an infectious diseases clinical pharmacy specialist, 4 clinical pharmacists, and a pharmacy technician. The clinical pharmacists provide consultations via telephone. Both patient- and trip-related information are gathered to assess the traveler's health risks. Recommendations are provided regarding food- and water-borne diseases, insect-borne diseases, sexually transmitted diseases, and diseases related to animal bites. Additionally, detailed information is provided on vaccines that may be needed to protect travelers against various diseases. The travel consult is documented electronically. A copy of the consult, along with a booklet that provides travel information, is mailed to the patient. Success of the CPITC is demonstrated in several ways. The clinic initially served Kaiser Permanente members in the Colorado Region. The service has expanded and now also provides travel consults to Kaiser Permanente members in the Northwest and Ohio Regions. Patient satisfaction is high, and significant cost-savings have been realized secondary to avoiding the use of unnecessary vaccinations and medications. The CPITC allows resources to be leveraged and provides one center where individuals trained in travel medicine provide information to members, thus improving efficiency and decreasing cost.

Expanding primary care capacity by reducing waste and improving the efficiency of care.

PubMed

Shipman, Scott A; Sinsky, Christine A

2013-11-01

Most solutions proposed for the looming shortage of primary care physicians entail strategies that fall into one of three categories: train more, lose fewer, or find someone else. A fourth strategy deserves more attention: waste less. This article examines the remarkable inefficiency and waste in primary care today and highlights practices that have addressed these problems. For example, delegating certain administrative tasks such as managing task lists in the electronic health record can give physicians more time to see additional patients. Flow managers who guide physicians from task to task throughout the clinical day have been shown to improve physicians' efficiency and capacity. Even something as simple as placing a printer in every exam room can save each physician twenty minutes per day. Modest but systemwide improvements could yield dramatic gains in physician capacity while potentially reducing physician burnout and its implications for the quality of care. If widely adopted, small efforts to empower nonphysicians, reengineer workflows, exploit technology, and update policies to eliminate wasted effort could yield the capacity for millions of additional patient visits per year in the United States.

Pyoderma gangrenosum: an exceptional complication of venous access device.

PubMed

La Marca, Sophie; Toussoun, Gilles; Ho Quoc, Christophe; Sebban, Henry; Delay, Emmanuel

2014-01-01

Pyoderma gangrenosum (PG) is a rare disease whose precise etiology remains unknown. It causes rapidly developing skin necrosis and can occur after surgery, or after a nonspecific external stimulus. This condition is difficult to diagnose because it often mimics a fulminant infection. We present a case of very significant local presentation of PG after placement of a venous access device. Fifteen days after placement, the patient developed extensive cutaneous ulcers and necrosis in the subclavicular area, which led to the misdiagnosis of infection. The device was removed and the patient was given antibiotics. Because there was no improvement following antibiotic treatment, combined with the worrying and extensive appearance of the skin and extremely intense pain, the diagnosis of PG was made. The patient was immediately treated with high-dose corticosteroids, resulting in rapid improvement of the lesions and relief of pain. PG should be considered in cases of extensive, antibiotic-resistant ulceration and treatment with corticosteroids should be initiated. Clinical improvement is usually dramatic, with almost immediate suppression of the pain and arrest of the lesion's progression. Early treatment is the best guarantee for an effective recovery.

Weight loss surgery improves quality of life in pediatric patients with osteogenesis imperfecta

PubMed Central

Zani, Augusto; Ford-Adams, Martha; Ratcliff, Megan; Bevan, Denise; Inge, Thomas H.; Desai, Ashish

2018-01-01

Background Osteogenesis imperfecta (OI) is an inherited disorder, which causes brittle bones resulting in recurrent fractures. The associated poor mobility of children with OI increases susceptibility to obesity, and obesity further dramatically limits mobility and increases fracture risk. Objectives The aim of this report was to describe outcomes of weight loss surgery (WLS) in two adolescents with severe obesity and OI. Setting Two University Hospitals (in the United Kingdom and in the United States). Methods Two cases of OI treated with WLS were identified. Pre- and post-operative anthropometric and biochemical data and clinical course were reviewed. Results In these 2 cases, preoperative Body Mass Index (BMI) values were 38 and 46 kg/m2. Following laparoscopic sleeve gastrectomy (LSG), BMI decreased by 55% and 60% by 26 and 24 months, respectively. There were no surgical complications and both patients experienced improvement in their mobility and ability to perform activities of daily living. Conclusions WLS effectively treated severe obesity in two OI patients and substantially improved mobility and quality of life, theoretically reducing fracture risk. PMID:26948942

A well-designed online transfusion reaction reporting system improves the estimation of transfusion reaction incidence and quality of care in transfusion practice.

PubMed

Yeh, Su-Peng; Chang, Ci-Wen; Chen, Ju-Chuan; Yeh, Wan-Chen; Chen, Pei-Chi; Chuang, Su-Jung; Lin, Chiou-Ping; Hsu, Ling-Nu; Chen, Han-Mih; Lu, Jang-Jih; Peng, Ching-Tien

2011-12-01

Recognizing and reporting a transfusion reaction is important in transfusion practice. However, the actual incidence of transfusion reactions is frequently underestimated. We designed an online transfusion reaction reporting system for nurses who take care of transfusion recipients. The common management before and after transfusion and the 18 most common transfusion reactions were itemized as tick boxes. We found the overall documented incidence of transfusion reaction increased dramatically, from 0.21% to 0.61% per unit of blood, after we started using an online reporting system. Overall, 94% (30/32) of nurses took only 1 week to become familiar with the new system, and 88% (28/32) considered the new system helpful in improving the quality of clinical transfusion care. By using an intranet connection, blood bank physicians can also identify patients who are having a reaction and provide appropriate recommendations immediately. A well-designed online reporting system may improve the ability to estimate the incidence of transfusion reactions and the quality of transfusion care.

SU-D-BRD-01: Cloud-Based Radiation Treatment Planning: Performance Evaluation of Dose Calculation and Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Na, Y; Kapp, D; Kim, Y

2014-06-01

Purpose: To report the first experience on the development of a cloud-based treatment planning system and investigate the performance improvement of dose calculation and treatment plan optimization of the cloud computing platform. Methods: A cloud computing-based radiation treatment planning system (cc-TPS) was developed for clinical treatment planning. Three de-identified clinical head and neck, lung, and prostate cases were used to evaluate the cloud computing platform. The de-identified clinical data were encrypted with 256-bit Advanced Encryption Standard (AES) algorithm. VMAT and IMRT plans were generated for the three de-identified clinical cases to determine the quality of the treatment plans and computationalmore » efficiency. All plans generated from the cc-TPS were compared to those obtained with the PC-based TPS (pc-TPS). The performance evaluation of the cc-TPS was quantified as the speedup factors for Monte Carlo (MC) dose calculations and large-scale plan optimizations, as well as the performance ratios (PRs) of the amount of performance improvement compared to the pc-TPS. Results: Speedup factors were improved up to 14.0-fold dependent on the clinical cases and plan types. The computation times for VMAT and IMRT plans with the cc-TPS were reduced by 91.1% and 89.4%, respectively, on average of the clinical cases compared to those with pc-TPS. The PRs were mostly better for VMAT plans (1.0 ≤ PRs ≤ 10.6 for the head and neck case, 1.2 ≤ PRs ≤ 13.3 for lung case, and 1.0 ≤ PRs ≤ 10.3 for prostate cancer cases) than for IMRT plans. The isodose curves of plans on both cc-TPS and pc-TPS were identical for each of the clinical cases. Conclusion: A cloud-based treatment planning has been setup and our results demonstrate the computation efficiency of treatment planning with the cc-TPS can be dramatically improved while maintaining the same plan quality to that obtained with the pc-TPS. This work was supported in part by the National Cancer Institute (1R01 CA133474) and by Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No.2009-00420)« less

Double-hairpin molecular-beacon-based amplification detection for gene diagnosis linked to cancer.

PubMed

Xu, Huo; Zhang, Rongbo; Li, Feng; Zhou, Yingying; Peng, Ting; Wang, Xuedong; Shen, Zhifa

2016-09-01

A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems. Graphical Abstract A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related gene KRAS detection based on the one-to-two stoichiometry. Without the help of any exogenous probe, the point mutation is easily screened, and the target DNA can be quantified down to 50 pM, indicating a dramatic improvement compared with traditional molecular beacons.

Nanotechnology-supported THz medical imaging

PubMed Central

Stylianou, Andreas; Talias, Michael A

2013-01-01

Over the last few decades, the achievements and progress in the field of medical imaging have dramatically enhanced the early detection and treatment of many pathological conditions. The development of new imaging modalities, especially non-ionising ones, which will improve prognosis, is of crucial importance. A number of novel imaging modalities have been developed but they are still in the initial stages of development and serious drawbacks obstruct them from offering their benefits to the medical field. In the 21 st century, it is believed that nanotechnology will highly influence our everyday life and dramatically change the world of medicine, including medical imaging. Here we discuss how nanotechnology, which is still in its infancy, can improve Terahertz (THz) imaging, an emerging imaging modality, and how it may find its way into real clinical applications. THz imaging is characterised by the use of non-ionising radiation and although it has the potential to be used in many biomedical fields, it remains in the field of basic research. An extensive review of the recent available literature shows how the current state of this emerging imaging modality can be transformed by nanotechnology. Innovative scientific concepts that use nanotechnology-based techniques to overcome some of the limitations of the use of THz imaging are discussed. We review a number of drawbacks, such as a low contrast mechanism, poor source performance and bulky THz systems, which characterise present THz medical imaging and suggest how they can be overcome through nanotechnology. Better resolution and higher detection sensitivity can also be achieved using nanotechnology techniques. PMID:24555052

Molecular and biological hallmarks of ageing.

PubMed

Aunan, J R; Watson, M M; Hagland, H R; Søreide, K

2016-01-01

Ageing is the inevitable time-dependent decline in physiological organ function that eventually leads to death. Age is a major risk factor for many of the most common medical conditions, such as cardiovascular disease, cancer, diabetes and Alzheimer's disease. This study reviews currently known hallmarks of ageing and their clinical implications. A literature search of PubMed/MEDLINE was conducted covering the last decade. Average life expectancy has increased dramatically over the past century and is estimated to increase even further. Maximum longevity, however, appears unchanged, suggesting a universal limitation to the human organism. Understanding the underlying molecular processes of ageing and health decline may suggest interventions that, if used at an early age, can prevent, delay, alleviate or even reverse age-related diseases. Hallmarks of ageing can be grouped into three main categories. The primary hallmarks cause damage to cellular functions: genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis. These are followed by antagonistic responses to such damage: deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Finally, integrative hallmarks are possible culprits of the clinical phenotype (stem cell exhaustion and altered intercellular communication), which ultimately contribute to the clinical effects of ageing as seen in physiological loss of reserve, organ decline and reduced function. The sum of these molecular hallmarks produces the clinical picture of the elderly surgical patient: frailty, sarcopenia, anaemia, poor nutrition and a blunted immune response system. Improved understanding of the ageing processes may give rise to new biomarkers of risk or prognosis, novel treatment targets and translational approaches across disciplines that may improve outcomes. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

A Toy Clinic Shop: Innovation Management in a Shin-Tai Elementary School

ERIC Educational Resources Information Center

Hong, Jon-Chao; Hwang, Ming-Yueh; Liang, Hwey-Wen; Chang, Hsin-Wu

2008-01-01

In Taiwan there is a declining birth rate and a dramatic increase in the elderly population. There is also the trend of using school space that would otherwise be left unused. The experimental project "Toy Clinic Shop in Elementary School" offers an innovative management model for elementary schools to address these developments. The…

Initial Results of a New Clinical Practice Model: Impact on Learners at Risk

ERIC Educational Resources Information Center

Wasburn-Moses, Leah; Noltemeyer, Amity L.; Schmitz, Kristin J.

2015-01-01

The last several years have seen a dramatic increase in interest surrounding the role of clinical experiences in enhancing the learning of teacher candidates. Further, pressure has intensified to demonstrate the impact of teacher candidates on P-12 learners. With these goals in mind, a model alternative school/university partnership was created,…

Management Development in Health Care: Exploring the Experiences of Clinical Nurse Managers

ERIC Educational Resources Information Center

Purcell, Laura; Milner, Brigid

2005-01-01

Purpose--The purpose of this paper is to investigate the dramatic reforms in the health service in recent years. Design/methodology/approach--Examines management development in health care, and explores the experiences of clinical nurse managers. Findings--Duplication of agencies and multiplication of roles have led to tensions in terms of both…

Zero to Three: Bulletin of the National Center for Clinical Infant Programs. Volume IX, Nos. 1-5, September, 1988-June, 1989.

ERIC Educational Resources Information Center

Zero to Three, 1989

1989-01-01

Five bulletins of the National Center for Clinical Infant Programs provide articles with the following titles and authors: "Motor Control as a Resource for Adaptive Coping" (G. Gordon Williamson et al.); "Fostering Emotional and Social Development in Infants with Disabilities" (Stanley Greenspan); "Dramatic Responses in a…

Primary Healthcare Provider Knowledge, Beliefs and Clinic-Based Practices Regarding Alternative Tobacco Products and Marijuana: A Qualitative Study

ERIC Educational Resources Information Center

Bascombe, Ta Misha S.; Scott, Kimberly N.; Ballard, Denise; Smith, Samantha A.; Thompson, Winifred; Berg, Carla J.

2016-01-01

Use prevalence of alternative tobacco products and marijuana has increased dramatically. Unfortunately, clinical guidelines have focused on traditional cigarettes with limited attention regarding these emerging public health issues. Thus, it is critical to understand how healthcare professionals view this issue and are responding to it. This…

Total knee arthroplasty in motivated patients with knee osteoarthritis and athletic activity approach type goals: a conceptual decision-making model.

PubMed

Nyland, John; Kanouse, Zachary; Krupp, Ryan; Caborn, David; Jakob, Rolie

2011-01-01

Knee osteoarthritis is one of the most common disabling medical conditions. With longer life expectancy the number of total knee arthroplasty (TKA) procedures being performed worldwide is projected to increase dramatically. Patient education, physical activity, bodyweight levels, expectations and goals regarding the ability to continue athletic activity participation are also increasing. For the subset of motivated patients with knee osteoarthritis who have athletic activity approach type goals, early TKA may not be the best knee osteoarthritis treatment option to improve satisfaction, quality of life and outcomes. The purpose of this clinical commentary is to present a conceptual decision-making model designed to improve the knee osteoarthritis treatment intervention outcome for motivated patients with athletic activity approach type goals. The model focuses on improving knee surgeon, patient and rehabilitation clinician dialogue by rank ordering routine activities of daily living and quality of life evoking athletic activities based on knee symptom exacerbation or re-injury risk. This process should help establish realistic patient expectations and goals for a given knee osteoarthritis treatment intervention that will more likely improve self-efficacy, functional independence, satisfaction and outcomes while decreasing the failure risk associated with early TKA.

A dramatic increase in the positive blood culture rates of Helicobacter cinaedi: the evidence of differential detection abilities between the Bactec and BacT/Alert systems.

PubMed

Miyake, Noriko; Chong, Yong; Nishida, Ruriko; Nagasaki, Yoji; Kibe, Yasushi; Kiyosuke, Makiko; Shimomura, Takeshi; Shimono, Nobuyuki; Shimoda, Shinji; Akashi, Koichi

2015-11-01

In our hospital, positive blood culture rates of Helicobacter cinaedi dramatically increased after introducing the Bactec system. A simulated culture model of H. cinaedi bacteremia demonstrated no positive signals using the BacT/Alert system, despite efficient growth in bottles. Clinically suspected H. cinaedi bacteremia should be monitored more closely when using the BacT/Alert system, preferably with subcultivation after 7days of incubation. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-E-E-05: Improving Contouring Precision and Consistency for Physicians-In-Training with Simple Lab Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Larson, D A

2015-06-15

Purpose: Target contouring for high-dose treatments such as radiosurgery of brain metastases is highly critical in eliminating marginal failure and reducing complications as shown by recent clinical studies. In order to improve contouring accuracy and practice consistency for the procedure, we introduced a self-assessed physics lab practice for the physicians-in-training. Methods: A set of commercially acquired high-precision PMMA plastic spheres were randomly embedded in a Styrofoam block and then scanned with the CT/MR via the clinical procedural imaging protocol. A group of first-year physicians-in-training (n=6) from either neurosurgery or radiation oncology department were asked to contour the scanned objects (diametermore » ranged from 0.4 cm to 3.8 cm). These user-defined contours were then compared with the ideal contour sets of object shape for self assessments to determine the maximum areas of the observed discrepancies and method of improvements. Results: The largest discrepancies from initial practice were consistently found to be located near the extreme longitudinal portions of the target for all the residents. Discrepancy was especially prominent when contouring small objects < 1.0 cm in diameters. For example, the mean volumes rendered from the initial contour data set differed from the ideal data set by 7.7%±6.6% for the participants (p> 0.23 suggesting agreement cannot be established). However, when incorporating a secondary imaging scan such as reconstructed coronal or sagittal images in a repeat practice, the agreement was dramatically improved yielding p<0.02 in agreement with the reference data set for all the participants. Conclusion: A simple physics lab revealed a common pitfall in contouring small metastatic brain tumors for radiosurgical procedures and provided a systematic tool for physicians-in-training in improving their clinical contouring skills. Dr Ma is current a board member of international stereotactic radiosurgical society.« less

Catalase abrogates β-lapachone-induced PARP1 hyperactivation-directed programmed necrosis in NQO1-positive breast cancers

PubMed Central

Bey, Erik A.; Reinicke, Kathryn E.; Srougi, Melissa C.; Varnes, Marie; Anderson, Vernon; Pink, John J.; Li, Long Shan; Patel, Malina; Cao, Lifen; Moore, Zachary; Rommel, Amy; Boatman, Michael; Lewis, Cheryl; Euhus, David M.; Bornmann, William G.; Buchsbaum, Donald J.; Spitz, Douglas R.; Gao, Jinming; Boothman, David A.

2013-01-01

Improving patient outcome by personalized therapy involves a thorough understanding of an agent’s mechanism of action. β-Lapachone (clinical forms, Arq501/Arq761) has been developed to exploit dramatic cancer-specific elevations in the phase II detoxifying enzyme, NAD(P)H:quinone oxidoreductase (NQO1). NQO1 is dramatically elevated in solid cancers, including primary and metastatic (e.g., triple-negative (ER-, PR-, Her2/Neu-)) breast cancers. To define cellular factors that influence the efficacy of β-lapachone using knowledge of its mechanism of action, we confirmed that NQO1 was required for lethality and mediated a futile redox cycle where ~120 moles of superoxide were formed per mole of β-lapachone in 5 min. β-Lapachone induced reactive oxygen species (ROS), stimulated DNA single strand break-dependent PARP1 hyperactivation, caused dramatic loss of essential nucleotides (NAD+/ATP) and elicited programmed necrosis in breast cancer cells. While PARP1 hyperactivation and NQO1 expression were major determinants of β-lapachone-induced lethality, alterations in catalase expression, including treatment with exogenous enzyme, caused marked cytoprotection. Thus, catalase is an important resistance factor, and highlights H2O2 as an obligate ROS for cell death from this agent. Exogenous superoxide dismutase (SOD) enhanced catalase-induced cytoprotection. β-Lapachone-induced cell death included AIF translocation from mitochondria to nuclei, TUNEL+ staining, atypical PARP1 cleavage, and GAPDH S-nitrosylation, which were abrogated by catalase. We predict that the ratio of NQO1:catalase activities in breast cancer versus associated normal tissue are likely to be the major determinants affecting the therapeutic window of β-lapachone and other NQO1 bioactivatable drugs. PMID:23883585

Insulin oedema and treatment-induced neuropathy occurring in a 20-year-old patient with Type 1 diabetes commenced on an insulin pump.

PubMed

Rothacker, K M; Kaye, J

2014-01-01

Oedema may occur following initiation or intensification of insulin therapy in patients with Type 1 and Type 2 diabetes. Mild oedema is thought to be not uncommon, but under-reported, whilst generalized oedema with involvement of serous cavities has rarely been described. Multiple pathogenic mechanisms have been proposed, including insulin-induced sodium and water retention. Patients at greater risk for insulin oedema include those with poor glycaemic control. Dramatic improvement in glycaemic control is also associated with sensory and autonomic neuropathy. We describe a case of generalized oedema occurring in a 20-year-old, low body weight patient with Type 1 diabetes with poor glycaemic control 3 days following commencement of an insulin pump; blood sugars had dramatically improved with this treatment. Alternative causes for oedema were excluded. Oedema slowly improved with insulin dose reduction with higher blood sugar targets plus frusemide treatment. Subsequent to oedema resolution, the patient unfortunately developed generalized neuropathic pain, thought to be another manifestation of rapid improvement in glycaemic control. Caution should be taken when a patient with diabetes that is poorly controlled has an escalation in therapy that may dramatically improve their blood sugar levels; this includes the initiation of an insulin pump. Clinicians and patients should be aware of the potential risk of insulin oedema, treatment-induced neuropathy and worsening of diabetic retinopathy in the setting of rapid improvement in glycaemic control. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Projections for insulin treatment for diabetics.

PubMed

Cao, Ying; Lam, Laura

2002-06-01

The evolution of insulin treatment of diabetes has dramatically changed the natural course of this disease. Modern recombinant DNA technology has brought about many new insulin analogues with improved pharmacokinetics, resulting in better glycemic control. In addition, improved insulin delivery systems, such as insulin pumps and pens, have been introduced to provide convenience and to enhance patient compliance. Efforts are currently being devoted to developing noninvasive insulin formulations, such as oral and pulmonary insulin. A number of products are at different stages of clinical trials. Meanwhile, the quest for a permanent cure for diabetes continues. The frontier of diabetes research has gone through a period of substantial expansion, with the emergence of new areas that include gene therapy, islet cell transplantation and diabetic vaccine. Technological breakthroughs, such as recombinant DNA, nanotechnology, microarray-aided genomics and proteomics, will provide more profound insights into the pathogenesis, and the immunological and biological basis of diabetes. Our growing knowledge in these areas will ultimately contribute to the discovery of preventive methods against or a cure for this disease.

A proteomic approach to obesity and type 2 diabetes

PubMed Central

López-Villar, Elena; Martos-Moreno, Gabriel Á; Chowen, Julie A; Okada, Shigeru; Kopchick, John J; Argente, Jesús

2015-01-01

The incidence of obesity and type diabetes 2 has increased dramatically resulting in an increased interest in its biomedical relevance. However, the mechanisms that trigger the development of diabetes type 2 in obese patients remain largely unknown. Scientific, clinical and pharmaceutical communities are dedicating vast resources to unravel this issue by applying different omics tools. During the last decade, the advances in proteomic approaches and the Human Proteome Organization have opened and are opening a new door that may be helpful in the identification of patients at risk and to improve current therapies. Here, we briefly review some of the advances in our understanding of type 2 diabetes that have occurred through the application of proteomics. We also review, in detail, the current improvements in proteomic methodologies and new strategies that could be employed to further advance our understanding of this pathology. By applying these new proteomic advances, novel therapeutic and/or diagnostic protein targets will be discovered in the obesity/Type 2 diabetes area. PMID:25960181

Drug-eluting versus bare-metal coronary stents: where are we now?

PubMed

Amoroso, Nicholas S; Bangalore, Sripal

2012-11-01

Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).

Improving CRISPR-Cas specificity with chemical modifications in single-guide RNAs.

PubMed

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Bruhn, Laurakay; Dellinger, Douglas J

2018-01-25

CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence') and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2'-O-methyl-3'-phosphonoacetate, or 'MP') incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs

PubMed Central

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Dellinger, Douglas J

2018-01-01

Abstract CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. PMID:29216382

Analogs, formulations and derivatives of imatinib: a patent review.

PubMed

Musumeci, Francesca; Schenone, Silvia; Grossi, Giancarlo; Brullo, Chiara; Sanna, Monica

2015-01-01

The Bcr-Abl inhibitor imatinib was approved in 2001 for chronic myeloid leukemia therapy, and dramatically changed the lives of patients affected by this disease. Since it also inhibits platelet derived growth factor receptor (PDGFR) and c-Kit, imatinib is used for various other tumors caused by abnormalities of one or both these two enzymes. This review presents an overview on imatinib formulations and derivatives, synthetic methodologies and therapeutic uses that have appeared in the patent literature since 2008. Innovative imatinib formulations, such as nanoparticles containing the drug, will improve its bioavailability. Moreover, oral solutions or high imatinib content tablets or capsules will improve patient compliance. Some solid formulations and innovative syntheses that have appeared in the last few years will reduce the cost of the drug, offering big advantages for poor countries. Some recently patented efficacious imatinib derivatives are in preclinical studies and could enter clinical trials in the next few years. Overall, Bcr-Abl inhibitors constitute a very appealing research field that can be expected to expand further.

Workflow in interventional radiology: nerve blocks and facet blocks

NASA Astrophysics Data System (ADS)

Siddoway, Donald; Ingeholm, Mary Lou; Burgert, Oliver; Neumuth, Thomas; Watson, Vance; Cleary, Kevin

2006-03-01

Workflow analysis has the potential to dramatically improve the efficiency and clinical outcomes of medical procedures. In this study, we recorded the workflow for nerve block and facet block procedures in the interventional radiology suite at Georgetown University Hospital in Washington, DC, USA. We employed a custom client/server software architecture developed by the Innovation Center for Computer Assisted Surgery (ICCAS) at the University of Leipzig, Germany. This software runs in an internet browser, and allows the user to record the actions taken by the physician during a procedure. The data recorded during the procedure is stored as an XML document, which can then be further processed. We have successfully gathered data on a number if cases using a tablet PC, and these preliminary results show the feasibility of using this software in an interventional radiology setting. We are currently accruing additional cases and when more data has been collected we will analyze the workflow of these procedures to look for inefficiencies and potential improvements.

Is there more to the clinical outcome in posttraumatic reconstruction of the inferior and medial orbital walls than accuracy of implant placement and implant surface contouring? A prospective multicenter study to identify predictors of clinical outcome.

PubMed

Zimmerer, Rüdiger M; Gellrich, Nils-Claudius; von Bülow, Sophie; Strong, Edward Bradley; Ellis, Edward; Wagner, Maximilian E H; Sanchez Aniceto, Gregorio; Schramm, Alexander; Grant, Michael P; Thiam Chye, Lim; Rivero Calle, Alvaro; Wilde, Frank; Perez, Daniel; Bittermann, Gido; Mahoney, Nicholas R; Redondo Alamillos, Marta; Bašić, Joanna; Metzger, Marc; Rasse, Michael; Dittman, Jan; Rometsch, Elke; Espinoza, Kathrin; Hesse, Ronny; Cornelius, Carl-Peter

2018-04-01

Reconstruction of orbital wall fractures is demanding and has improved dramatically with the implementation of new technologies. True-to-original accuracy of reconstruction has been deemed essential for good clinical outcome, and reasons for unfavorable clinical outcome have been researched extensively. However, no detailed analysis on the influence of plate position and surface contour on clinical outcome has yet been published. Data from a previous study were used for an ad-hoc analysis to identify predictors for unfavorable outcome, defined as diplopia or differences in globe height and/or globe projection of >2 mm. Presumed predictors were implant surface contour, aberrant implant dimension or position, accuracy of reconstructed orbital volume, and anatomical fracture topography according to the current AO classification. Neither in univariable nor in multivariable regression models were unfavorable clinical outcomes associated with any of the presumed radiological predictors, and no association of the type of implant, i.e., standard preformed, CAD-based individualized and non-CAD-based individualized with its surface contour could be shown. These data suggest that the influence of accurate mechanical reconstruction on clinical outcomes may be less predictable than previously believed, while the role of soft-tissue-related factors may have been underestimated. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Continuous Quality Improvement: A Roadmap for Rural School Improvement.

ERIC Educational Resources Information Center

Kilmer, Lloyd C.

A case study documented a continuous quality improvement approach to school improvement in a rural Nebraska high school over a 2-year period. Data gathered from surveys, portfolios, pilot results, and test scores indicated that the changes during the 2-year period were not dramatic, but significant and consistent with the Total Quality literature.…

Le Fort-based maxillofacial transplantation: current state of the art and a refined technique using orthognathic applications.

PubMed

Gordon, Chad R; Susarla, Srinivas M; Peacock, Zachary S; Kaban, Leonard B; Yaremchuk, Michael J

2012-01-01

Following encouraging results from the first 6 maxillofacial allotransplants, there has been a dramatic rise in interest worldwide. Numerous groups are now devoting resources to increase the frequency of these complex procedures, and with this, the craniomaxillofacial surgeon should become familiar with the emerging state of the art. This article reviews the evolution of Le Fort-based cadaveric studies pertaining to maxillofacial allotransplantation, briefly describes the clinical reports through 2010, and introduces a refined technique applying orthognathic applications. Preliminary studies over the last 5 years have highlighted the challenges associated with transplanting skeletal components, and clinical results presented thus far have been extremely promising. However, a notable area for improvement is suboptimal facial-skeletal harmony and profile in the context of sagittal skeletal projection and maxillomandibular relation. To our knowledge, orthognathic planning as applied to osteocutaneous face transplantation has not been described. Many recipients seen thus far demonstrate some degree of malocclusion and suboptimal harmony, as expected, given the donor-to-recipient skeletal/jaw discrepancies. Given that the goal is to improve function as well as form, the importance of orthognathic planning cannot be overstated with respect to optimizing harmony, profile, and occlusion. Preoperative planning, including generation of donor/recipient dental cast models, as described herein for the first time, is essential.

Enhancing Outcomes for Outpatient Percutaneous Coronary Interventions

PubMed Central

Spruce, Kevin; Butler, Chondra

2017-01-01

Purpose and Objectives: A quality improvement project was conducted to create a sustainable continuum of care for increased volumes of outpatients receiving percutaneous coronary interventions. Dramatic growth exposed system vulnerabilities and left staff overwhelmed. Four postinterventional project objectives included reducing preprocedural preparation times, reducing bleeding complications, reducing hospital length of stay, and collectively increasing patient satisfaction. Description of the Project: Amidst creating a specialized postintervention coronary recovery area and acquiring and training existing preregistration and recovery nurses, a fragmented system of care was united. The clinical nurse specialist–led project used a systematic and evidence-based implementation process to harmoniously acclimate perioperative staff. An evaluation process further defined new opportunities to support a growing service line. Outcomes: Postimplementation data were collected over a 3-month period. An overall improvement was found in all targeted objectives, despite an upsurge in case volumes. A moderately significant correlation (r [105] = 0.424, P < .001) was found between bleeding occurrences and hospital length of stay. Conclusion: The synergy between interdepartmental collaboration and strategic staffing reallocation was shown to be invaluable to alleviate procedural areas of service, such as the cardiac catheterization laboratory. As a project champion, the clinical nurse specialist is an essential catalyst to identify and creatively surmount system-level challenges. PMID:28991015

HIV, tuberculosis, and noncommunicable diseases: what is known about the costs, effects, and cost-effectiveness of integrated care?

PubMed

Hyle, Emily P; Naidoo, Kogieleum; Su, Amanda E; El-Sadr, Wafaa M; Freedberg, Kenneth A

2014-09-01

Unprecedented investments in health systems in low- and middle-income countries (LMICs) have resulted in more than 8 million individuals on antiretroviral therapy. Such individuals experience dramatically increased survival but are increasingly at risk of developing common noncommunicable diseases (NCDs). Integrating clinical care for HIV, other infectious diseases, and NCDs could make health services more effective and provide greater value. Cost-effectiveness analysis is a method to evaluate the clinical benefits and costs associated with different health care interventions and offers guidance for prioritization of investments and scale-up, especially as resources are increasingly constrained. We first examine tuberculosis and HIV as 1 example of integrated care already successfully implemented in several LMICs; we then review the published literature regarding cervical cancer and depression as 2 examples of NCDs for which integrating care with HIV services could offer excellent value. Direct evidence of the benefits of integrated services generally remains scarce; however, data suggest that improved effectiveness and reduced costs may be attained by integrating additional services with existing HIV clinical care. Further investigation into clinical outcomes and costs of care for NCDs among people living with HIV in LMICs will help to prioritize specific health care services by contributing to an understanding of the affordability and implementation of an integrated approach.

Juvenile selective vitamin B₁₂ malabsorption: 50 years after its description-10 years of genetic testing.

PubMed

Gräsbeck, Ralph; Tanner, Stephan M

2011-09-01

Fifty years have passed since the description of juvenile selective malabsorption of cobalamin (Cbl). Quality of life improvements have dramatically reduced the incidence of parasite-induced or nutritional Cbl deficiency. Consequently, inherited defects have become a leading cause of Cbl deficiency in children, which is not always expressed as anemia. Unfortunately, the gold standard for clinical diagnosis, the Schilling test, has increasingly become unavailable, and replacement tests are only in their infancy. Genetic testing is complicated by genetic heterogeneity and differential diagnosis. This review documents the history, research, and advances in genetics that have elucidated the causes of juvenile Cbl malabsorption. Genetic research has unearthed many cases in the past decade, mostly in Europe and North America, often among immigrants from the Middle East or North Africa. Lack of suitable clinical testing potentially leaves many patients inadequately diagnosed. The consequences of suboptimal Cbl levels for neurological development are well documented. By raising awareness, we wish to push for fast track development of better clinical tools and suitable genetic testing. Clinical awareness must include attention to ethnicity, a sensitive topic but effective for fast diagnosis. The treatment with monthly parenteral Cbl for life offers a simple and cost-effective solution once proper diagnosis is made.

Ethics in neonatology: a look over Europe.

PubMed

Guimarães, Hercilia; Rocha, Gustavo; Almeda, Filipe; Brites, Marta; Van Goudoever, Johannes B; Iacoponi, Francesca; Bellieni, Carlo; Buonocore, Giuseppe

2012-07-01

Advances in perinatal medicine have dramatically improved neonatal survival. End-of-life decision making for newborns with adverse prognosis is an ethical challenge, the ethical issues are controversial and little evidence exists on attitudes and values in Europe. to assess the attitudes of the neonatal departments in perinatal clinical practice in the hospitals of European countries. a questionnaire was send to 55 NICUs from 19 European countries. Forty five (81.8%) NICUs were Level III. Religion was Christian in 90.7% and we observed that in north countries the religion is more influent on clinical decisions (p = 0.032). Gestational age was considered with no significant difference for clinical investment. North countries consider birth weight (p = 0.011) and birth weight plus gestational age (p = 0.024) important for clinical investment. In north countries ethical questions should not prevail when the decision is made (p = 0.049) and from an ethical point of view, there is no difference between withdraw a treatment and do not initiate the treatment (p = 0.029). More hospitals in south countries administer any analgesia (p = 0.007). When the resuscitation is not successful 96.2% provide comfort care. Our study reveals that cultural and religious differences influenced ethical attitudes in NICUs of the European countries.

Rectal cancer surgery: a brief history.

PubMed

Galler, Avi S; Petrelli, Nicholas J; Shakamuri, Shanthi P

2011-12-01

In the last 250 years, the treatment of rectal cancer has changed dramatically. Once considered an incurable disease, combined modality therapy has improved mortality from 100% to less than 4% for locally advanced rectal cancer. This dramatic reduction paralleled surgical techniques based on a growing understanding of anatomy and disease pathology. In order to understand modern treatment, it is necessary to recognize the achievements of preceding surgeons. Copyright © 2010 Elsevier Ltd. All rights reserved.

Dramatic reduction of culture time of Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Ghodbane, Ramzi; Raoult, Didier; Drancourt, Michel

2014-02-01

Mycobacterium tuberculosis culture, a critical technique for routine diagnosis of tuberculosis, takes more than two weeks. Here, step-by-step improvements in the protocol including a new medium, microaerophlic atmosphere or ascorbic-acid supplement and autofluorescence detection dramatically shortened this delay. In the best case, primary culture and rifampicin susceptibility testing were achieved in 72 hours when specimens were inoculated directly on the medium supplemented by antibiotic at the beginning of the culture.

Realistic wave-optics simulation of X-ray phase-contrast imaging at a human scale

PubMed Central

Sung, Yongjin; Segars, W. Paul; Pan, Adam; Ando, Masami; Sheppard, Colin J. R.; Gupta, Rajiv

2015-01-01

X-ray phase-contrast imaging (XPCI) can dramatically improve soft tissue contrast in X-ray medical imaging. Despite worldwide efforts to develop novel XPCI systems, a numerical framework to rigorously predict the performance of a clinical XPCI system at a human scale is not yet available. We have developed such a tool by combining a numerical anthropomorphic phantom defined with non-uniform rational B-splines (NURBS) and a wave optics-based simulator that can accurately capture the phase-contrast signal from a human-scaled numerical phantom. Using a synchrotron-based, high-performance XPCI system, we provide qualitative comparison between simulated and experimental images. Our tool can be used to simulate the performance of XPCI on various disease entities and compare proposed XPCI systems in an unbiased manner. PMID:26169570

VGKC positive autoimmune encephalopathy mimicking dementia

PubMed Central

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O’ Toole, Orna

2011-01-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan’s syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment. PMID:22674939

Remarkable motor recovery after riboflavin therapy in adult-onset Brown—Vialetto—Van Laere syndrome

PubMed Central

Bashford, James A; Chowdhury, Fahmida A; Shaw, Chris E

2017-01-01

The clinical diagnosis of Brown—Vialetto—Van Laere syndrome in this woman with rapidly progressive pontobulbar palsy led to empirical high-dose oral riboflavin (1200 mg/day) therapy. This resulted in a dramatic improvement in her motor function from being anarthric, dysphagic, tetraparetic and in ventilatory failure to living independently with mild dysarthria and distal limb weakness. DNA sequencing of the SLC52A3 gene found compound heterozygous C-terminus mutations, V413A1/D461Y, consistent with recent reports of mutations within the riboflavin transporter genes (SLC52A2 and SLC52A3) in this condition. Early diagnosis and empirical riboflavin therapy can lead to major motor recovery in this condition, that can be sustained with long-term maintenance therapy. PMID:27777325

Realistic wave-optics simulation of X-ray phase-contrast imaging at a human scale

NASA Astrophysics Data System (ADS)

Sung, Yongjin; Segars, W. Paul; Pan, Adam; Ando, Masami; Sheppard, Colin J. R.; Gupta, Rajiv

2015-07-01

X-ray phase-contrast imaging (XPCI) can dramatically improve soft tissue contrast in X-ray medical imaging. Despite worldwide efforts to develop novel XPCI systems, a numerical framework to rigorously predict the performance of a clinical XPCI system at a human scale is not yet available. We have developed such a tool by combining a numerical anthropomorphic phantom defined with non-uniform rational B-splines (NURBS) and a wave optics-based simulator that can accurately capture the phase-contrast signal from a human-scaled numerical phantom. Using a synchrotron-based, high-performance XPCI system, we provide qualitative comparison between simulated and experimental images. Our tool can be used to simulate the performance of XPCI on various disease entities and compare proposed XPCI systems in an unbiased manner.

Developments in neonatal care and nursing responses.

PubMed

Healy, Patricia; Fallon, Anne

This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.

The Diabetes Management Education Program in South Texas: An Economic and Clinical Impact Analysis.

PubMed

Kash, Bita A; Lin, Szu-Hsuan; Baek, Juha; Ohsfeldt, Robert L

2017-01-01

Diabetes is a major chronic disease that can lead to serious health problems and high healthcare costs without appropriate disease management and treatment. In the United States, the number of people diagnosed with diabetes and the cost for diabetes treatment has dramatically increased over time. To improve patients' self-management skills and clinical outcomes, diabetes management education (DME) programs have been developed and operated in various regions. This community case study explores and calculates the economic and clinical impacts of expanding a model DME program into 26 counties located in South Texas. The study sample includes 355 patients with type 2 diabetes and a follow-up hemoglobin A1c level measurement among 1,275 individuals who participated in the DME program between September 2012 and August 2013. We used the Gilmer's cost differentials model and the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine methodology to predict 3-year healthcare cost savings and 10-year clinical benefits of implementing a DME program in the selected 26 Texas counties. Changes in estimated 3-year cost and the estimated treatment effect were based on baseline hemoglobin A1c level. An average 3-year reduction in medical treatment costs per program participant was $2,033 (in 2016 dollars). The total healthcare cost savings for the 26 targeted counties increases as the program participation rate increases. The total projected cost saving ranges from $12 million with 5% participation rate to $185 million with 75% participation rate. A 10-year outlook on additional clinical benefits associated with the implementation and expansion of the DME program at 60% participation is estimated to result in approximately 4,838 avoided coronary heart disease cases and another 392 cases of avoided strokes. The implementation of this model DME program in the selected 26 counties would contribute to substantial healthcare cost savings and clinical benefits. Organizations that provide DME services may benefit from reduction in medical treatment costs and improvement in clinical outcomes for populations with diabetes.

Automation in drug inventory management saves personnel time and budget.

PubMed

Awaya, Toshio; Ohtaki, Ko-ichi; Yamada, Takehiro; Yamamoto, Kuniko; Miyoshi, Toshiyuki; Itagaki, Yu-ichi; Tasaki, Yoshikazu; Hayase, Nobumasa; Matsubara, Kazuo

2005-05-01

Automation in the drug distribution processes is helpful to pharmacists in creating new clinical services. We have ameliorated the drug inventory control system seamlessly connected with the physician order-entry system. This control system application, named Artima, allows inventory functions to be faster and more efficient in real time. The medicines used in our hospital are automatically fixed and arranged to sold-packages, and are ordered from each wholesaler by a fax-modem every day. Artima can search the lot number and expiration date of drug in the purchase and delivery records. These functions are powerful and useful in patient's safety and cost containment. We surveyed the inventory amount stored in the computer database, and evaluated time required for inventory management by tabulating working records of employees during past decades. Inventory decreased by 70% along with the continuous improvement of the system during the past decade. The workload in the inventory management in each section of the Pharmacy Department as well as in clinical units was dramatically reduced after the implementation of this system. The automation system in the drug inventory management allows creating new clinical positions for pharmacists. This system also could pay for itself in time.

Mobile Devices for the Remote Acquisition of Physiological and Behavioral Biomarkers in Psychiatric Clinical Research

PubMed Central

Adams, Zachary; McClure, Erin A.; Gray, Kevin M.; Danielson, Carla Kmett; Treiber, Frank A.; Ruggiero, Kenneth J.

2016-01-01

Psychiatric disorders are linked to a variety of biological, psychological, and contextual causes and consequences. Laboratory studies have elucidated the importance of several key physiological and behavioral biomarkers in the study of psychiatric disorders, but much less is known about the role of these biomarkers in naturalistic settings. These gaps are largely driven by methodological barriers to assessing biomarker data rapidly, reliably, and frequently outside the clinic or laboratory. Mobile health (mHealth) tools offer new opportunities to study relevant biomarkers in concert with other types of data (e.g., self-reports, global positioning system data). This review provides an overview on the state of this emerging field and describes examples from the literature where mHealth tools have been used to measure a wide array of biomarkers in the context of psychiatric functioning (e.g., psychological stress, anxiety, autism, substance use). We also outline advantages and special considerations for incorporating mHealth tools for remote biomarker measurement into studies of psychiatric illness and treatment and identify several specific opportunities for expanding this promising methodology. Integrating mHealth tools into this area may dramatically improve psychiatric science and facilitate highly personalized clinical care of psychiatric disorders. PMID:27814455

A case of allergic bronchopulmonary aspergillosis successfully treated with mepolizumab.

PubMed

Terashima, Takeshi; Shinozaki, Taro; Iwami, Eri; Nakajima, Takahiro; Matsuzaki, Tatsu

2018-03-27

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard therapy for ABPA, but long-term use of systemic corticosteroids often causes serious side effects. A 64-year-old woman was diagnosed with ABPA based on a history of bronchial asthma (from 40 years of age), elevated total IgE, the presence of serum precipitating antibodies and elevated specific IgE antibody to A. fumigatus, and pulmonary infiltration. Bronchoscopy showed eosinophilic mucoid impaction. Systemic corticosteroid therapy was initiated, and her symptoms disappeared. Peripheral eosinophilia and pulmonary infiltration recurred five months after cessation of corticosteroid treatment. Systemic corticosteroids were re-initiated and itraconazole was added as an anti-fungal agent. The patient was free of corticosteroids, aside from treatment with a short course of systemic corticosteroids for asthma exacerbation, and clinically stable with itraconazole and asthma treatments for 3 years. In 2017, she experienced significant deterioration. Laboratory examination revealed marked eosinophilia (3017/μL) and a chest computed tomography (CT) scan demonstrated pulmonary infiltration in the left upper lobe and mucoid impaction in both lower lobes. The patient was treated with high-dose inhaled corticosteroid/long-acting beta-agonist, a long-acting muscarinic antagonist, a leukotriene receptor antagonist, and theophylline; spirometry revealed a forced expiratory volume in 1 s (FEV 1 ) of 1.01 L. An uncontrolled asthma state was indicated by an Asthma Control Test (ACT) score of 18. Mepolizumab, 100 mg every 4 weeks, was initiated for the treatment of severe bronchial asthma with ABPA exacerbation. Bronchial asthma symptoms dramatically improved, and ACT score increased to 24, by 4 weeks after mepolizumab treatment. Peripheral eosinophil count decreased to 174/μL. Spirometry revealed improvement of lung function (FEV 1 : 1.28 L). A chest CT scan demonstrated the disappearance of pulmonary infiltration and mucoid impaction. To our knowledge, this is the first case of ABPA to be treated with mepolizumab. Dramatic improvements were observed in symptoms, lung function, peripheral eosinophil counts, and chest images. Mepolizumab could serve as an alternative treatment with the potential to provide a systemic corticosteroid-sparing effect.

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

PubMed

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

A case of organic brain syndrome following head injury successfully treated with carbamazepine.

PubMed

Bouvy, P F; van de Wetering, B J; Meerwaldt, J D; Bruijn, J B

1988-03-01

A case of organic brain syndrome occurring in relation to psychological stress 2 years after a severe head injury is described. Treatment with haloperidol resulted only in slight improvement. A dramatic improvement was achieved with carbamazepine.

Dissemination and Adoption of Comparative Effectiveness Research Findings When Findings Challenge Current Practices

PubMed Central

Schneider, Eric C.; Timbie, Justin W.; Fox, D. Steven; Van Busum, Kristin R.; Caloyeras, John P.

2013-01-01

Abstract Insufficient evidence regarding the effectiveness of medical treatments has been identified as a key source of inefficiency in the U.S. healthcare system. Variation in the use of diagnostic tests and treatments for patients with similar symptoms or conditions has been attributed to clinical uncertainty, since the published scientific evidence base does not provide adequate information to determine which treatments are most effective for patients with specific clinical needs. The federal government has made a dramatic investment in comparative effectiveness research (CER), with the expectation that CER will influence clinical practice and improve the efficiency of healthcare delivery. To do this, CER must provide information that supports fundamental changes in healthcare delivery and informs the choice of diagnostic and treatment strategies. This article summarizes findings from a qualitative analysis of the factors that impede the translation of CER into clinical practice and those that facilitate it. A case-study methodology is used to explore the extent to which these factors led to changes in clinical practice following five recent key CER studies. The enabling factors and barriers to translation for each study are discussed, the root causes for the failure of translation common to the studies are synthesized, and policy options that may optimize the impact of future CER—particularly CER funded through the American Recovery and Reinvestment Act of 2009—are proposed. PMID:28083277

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations*

PubMed Central

Lynagh, Timothy; Lynch, Joseph W.

2010-01-01

The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light-activated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human α1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G α1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID:20308070

Hypertrophic obstructive cardiomyopathy: the Mayo Clinic experience.

PubMed

Kotkar, Kunal D; Said, Sameh M; Dearani, Joseph A; Schaff, Hartzell V

2017-07-01

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by left ventricular hypertrophy in the absence of other etiologies. Clinical presentation may vary from asymptomatic to sudden cardiac death. Medical treatment is the first-line therapy for symptomatic patients. Extended left ventricular septal myectomy is the procedure of choice if medical treatment is unsuccessful or intolerable. More than 3,000 patients have had septal myectomy for HCM at the Mayo Clinic (MN, USA) from 1993 to 2016. Risk of hospital death after isolated septal myectomy for obstructive HCM is <1% and is similar to the risk of operation for elective mitral valve repair. Complications, such as complete heart block requiring permanent pacemaker, are uncommon (2%), although partial or complete left bundle branch block is a frequent finding on the postoperative ECG. Relief of left ventricular outflow tract (LVOT) obstruction with septal myectomy dramatically improves symptoms and exercise capacity in symptomatic patients with obstructive HCM. More than 90% of severely symptomatic patients have improvement by at least two functional classes, and reduction of outflow gradients by myectomy decreases or eliminates symptoms of dyspnea, angina and/or syncope. Basal obstruction with systolic anterior motion (SAM) is treated by transaortic myectomy. The transapical approach was applied in 115 patients with obstructive midventricular and apical variants of HCM between 1993 and 2012. All patients with midventricular obstruction had gradient relief and none developed an apical aneurysm or ventricular septal defect. Recurrent obstruction after satisfactory myectomy was rare. Septal myectomy effectively and definitively relieves LVOT obstruction and cardiac symptoms in patients with obstructive HCM. In experienced centers, early mortality for isolated septal myectomy is less than 1%, and overall results are excellent and continue to improve in the current era.

Use of ethylene-vinyl alcohol copolymer as a liquid embolic agent to treat a peripheral arteriovenous malformation in a dog

PubMed Central

Culp, William T. N.; Glaiberman, Craig B.; Pollard, Rachel E.; Wisner, Erik R.

2015-01-01

Case Description An 11-year-old castrated male Tibetan Mastiff was evaluated because of a visibly enlarged blood vessel and progressively worsening swelling of the right hind limb. Clinical Findings On physical examination, the right hind limb was markedly larger than the left hind limb and the dog was minimally weight bearing on the affected limb. A bruit was auscultated over the affected region. Ultrasonography of the tarsal region of the right hind limb revealed an artery with turbulent flow that communicated with venous drainage. A CT scan confirmed the presence of an arteriovenous malformation (AVM). Treatment and Outcome Embolization of the AVM with a liquid embolic agent (ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide) was elected. An arteriogram was performed prior to treatment and delineated the vessels that were targeted for embolization. The embolic agent was infused into the AVM, and a postinjection arteriogram confirmed complete occlusion of the AVM nidus and normal arterial flow to the paw with subsequent normal venous drainage. The circumference of the abnormal paw was 51 cm before the procedure and 22.9 cm at 4 weeks after the procedure. Additionally, the gait of the dog dramatically improved. No complications associated with the procedure developed. Clinical Relevance Peripheral AVMs in dogs are uncommon, and described treatment options are limited and generally associated with serious morbidity. A liquid embolic agent, ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide, was successfully administered in this case, and no morbidity was observed secondary to the procedure. Clinical success was characterized by substantial improvement in limb swelling and marked improvement in the gait of the dog. PMID:24984133

Gender Issues in Gifted Achievement: Are Girls Making Inroads While Boys Fall Behind?

ERIC Educational Resources Information Center

Rimm, Sylvia B.

2015-01-01

School and life achievement patterns for girls and women differ from those of boys and men. While girls have made dramatic progress in school, they need to be inspired to connect to lifelong achievement. Both research and clinical work at the Ohio-based Family Achievement Clinic find that more boys than girls underachieve in school. There is much…

Angiotensin-converting enzyme inhibitor use by older adults is associated with greater functional responses to exercise.

PubMed

Buford, Thomas W; Manini, Todd M; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D; Nayfield, Susan; Stafford, Randall S; Church, Timothy S; Pahor, Marco; Carter, Christy S

2012-07-01

To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. Four academic research centers within the United States. Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91).The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Angiotensin-Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise

PubMed Central

Buford, Thomas W.; Manini, Todd M.; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D.; Nayfield, Susan; Stafford, Randall S.; Church, Timothy S.; Pahor, Marco; Carter, Christy S.

2013-01-01

OBJECTIVES To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. DESIGN Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. SETTING Four academic research centers within the United States. PARTICIPANTS Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. INTERVENTION A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). MEASUREMENTS Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). RESULTS Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). CONCLUSION For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. PMID:22726232

Changing Landscape of Congenital Heart Disease.

PubMed

Bouma, Berto J; Mulder, Barbara J M

2017-03-17

Congenital heart disease is the most frequently occurring congenital disorder affecting ≈0.8% of live births. Thanks to great efforts and technical improvements, including the development of cardiopulmonary bypass in the 1950s, large-scale repair in these patients became possible, with subsequent dramatic reduction in morbidity and mortality. The ongoing search for progress and the growing understanding of the cardiovascular system and its pathophysiology refined all aspects of care for these patients. As a consequence, survival further increased over the past decades, and a new group of patients, those who survived congenital heart disease into adulthood, emerged. However, a large range of complications raised at the horizon as arrhythmias, endocarditis, pulmonary hypertension, and heart failure, and the need for additional treatment became clear. Technical solutions were sought in perfection and creation of new surgical techniques by developing catheter-based interventions, with elimination of open heart surgery and new electronic devices enabling, for example, multisite pacing and implantation of internal cardiac defibrillators to prevent sudden death. Over time, many pharmaceutical studies were conducted, changing clinical treatment slowly toward evidence-based care, although results were often limited by low numbers and clinical heterogeneity. More attention has been given to secondary issues like sports participation, pregnancy, work, and social-related difficulties. The relevance of these issues was already recognized in the 1970s when the need for specialized centers with multidisciplinary teams was proclaimed. Finally, research has become incorporated in care. Results of intervention studies and registries increased the knowledge on epidemiology of adults with congenital heart disease and their complications during life, and at the end, several guidelines became easily accessible, guiding physicians to deliver care appropriately. Over the past decades, the landscape of adult congenital heart disease has changed dramatically, which has to be continued in the future. © 2017 American Heart Association, Inc.

Teacher Evaluation: Principals' Insights and Suggestions for Improvement

ERIC Educational Resources Information Center

Kersten, Thomas A.; Israel, Marla S.

2005-01-01

In the twenty-first century, school improvement is the focal point for educational leadership, in which the school building administrator is recognized as the catalyst for this necessary improvement. Within the area of teacher evaluation, the evaluation tools, along with the amount of time, format, and feedback, have changed dramatically from the…

Achieving Dramatic School Improvement: An Exploratory Study. A Cross-Site Analysis from the Evaluation of Comprehensive School Reform Program Implementation and Outcomes Study

ERIC Educational Resources Information Center

Aladjem, Daniel K.; Birman, Beatrice F.; Orland, Martin; Harr-Robins, Jenifer; Heredia, Alberto; Parrish, Thomas B.; Ruffini, Stephen J.

2010-01-01

This exploratory study describes approaches to improving schools through retrospective, in-depth qualitative case studies. To select schools to be examined, the authors sought to identify Comprehensive School Reform (CSR) schools demonstrating two distinctive patterns of improved student achievement between 2000 and 2005, rapid-improvement (i.e.,…

An educational implementation of a cancer pain algorithm for ambulatory care.

PubMed

Du Pen, A R; Du Pen, S; Hansberry, J; Miller-Kraybill, B; Millen, J; Everly, R; Hansen, N; Syrjala, K

2000-12-01

Algorithms are proposed as a means of operationalizing guidelines or standards for cancer pain management. Professional education is used as the means to translate knowledge into practice. Outcomes measurement is the gold standard for validating improvement. This study used an educational intervention to transfer knowledge on implementing a previously tested algorithm for cancer pain management into community outpatient oncology clinics and, subsequently, measuring patient outcomes. Physicians and nurses from 9 Puget Sound clinics were randomized by institution blocks to either "training" or "no training." Role model physician/nurse teams were the core faculty for a day-long seminar. Written reference materials and documentation tools were provided to the trained physician/nurse teams. A total of 105 patients of trained and untrained providers were accrued and assessed over 4 months. Patients of trained providers had a significant reduction in usual pain over the 4 months of data collection compared with patients of untrained providers (t = 2.0; p = .05). Improvements were modest in the prescription of opioid analgesics and dramatic in the prescription of co-analgesics for neuropathic pain. There was a clear deterioration in the impact of the training over time. The most significant effect occurred within the first 140 days after the intervention and was followed by a gradual return to baseline practice. In conclusion, algorithmic interventions can be successfully transferred into community practice, but further work must be performed to develop methods for securing retention of knowledge and maintaining improved outcomes.

Real-time feedback can improve infant manikin cardiopulmonary resuscitation by up to 79%--a randomised controlled trial.

PubMed

Martin, Philip; Theobald, Peter; Kemp, Alison; Maguire, Sabine; Maconochie, Ian; Jones, Michael

2013-08-01

European and Advanced Paediatric Life Support training courses. Sixty-nine certified CPR providers. CPR providers were randomly allocated to a 'no-feedback' or 'feedback' group, performing two-thumb and two-finger chest compressions on a "physiological", instrumented resuscitation manikin. Baseline data was recorded without feedback, before chest compressions were repeated with one group receiving feedback. Indices were calculated that defined chest compression quality, based upon comparison of the chest wall displacement to the targets of four, internationally recommended parameters: chest compression depth, release force, chest compression rate and compression duty cycle. Baseline data were consistent with other studies, with <1% of chest compressions performed by providers simultaneously achieving the target of the four internationally recommended parameters. During the 'experimental' phase, 34 CPR providers benefitted from the provision of 'real-time' feedback which, on analysis, coincided with a statistical improvement in compression rate, depth and duty cycle quality across both compression techniques (all measures: p<0.001). Feedback enabled providers to simultaneously achieve the four targets in 75% (two-finger) and 80% (two-thumb) of chest compressions. Real-time feedback produced a dramatic increase in the quality of chest compression (i.e. from <1% to 75-80%). If these results transfer to a clinical scenario this technology could, for the first time, support providers in consistently performing accurate chest compressions during infant CPR and thus potentially improving clinical outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Computer-assisted adjuncts for aneurysmal morphologic assessment: toward more precise and accurate approaches

NASA Astrophysics Data System (ADS)

Rajabzadeh-Oghaz, Hamidreza; Varble, Nicole; Davies, Jason M.; Mowla, Ashkan; Shakir, Hakeem J.; Sonig, Ashish; Shallwani, Hussain; Snyder, Kenneth V.; Levy, Elad I.; Siddiqui, Adnan H.; Meng, Hui

2017-03-01

Neurosurgeons currently base most of their treatment decisions for intracranial aneurysms (IAs) on morphological measurements made manually from 2D angiographic images. These measurements tend to be inaccurate because 2D measurements cannot capture the complex geometry of IAs and because manual measurements are variable depending on the clinician's experience and opinion. Incorrect morphological measurements may lead to inappropriate treatment strategies. In order to improve the accuracy and consistency of morphological analysis of IAs, we have developed an image-based computational tool, AView. In this study, we quantified the accuracy of computer-assisted adjuncts of AView for aneurysmal morphologic assessment by performing measurement on spheres of known size and anatomical IA models. AView has an average morphological error of 0.56% in size and 2.1% in volume measurement. We also investigate the clinical utility of this tool on a retrospective clinical dataset and compare size and neck diameter measurement between 2D manual and 3D computer-assisted measurement. The average error was 22% and 30% in the manual measurement of size and aneurysm neck diameter, respectively. Inaccuracies due to manual measurements could therefore lead to wrong treatment decisions in 44% and inappropriate treatment strategies in 33% of the IAs. Furthermore, computer-assisted analysis of IAs improves the consistency in measurement among clinicians by 62% in size and 82% in neck diameter measurement. We conclude that AView dramatically improves accuracy for morphological analysis. These results illustrate the necessity of a computer-assisted approach for the morphological analysis of IAs.

The integration of psychology in pediatric oncology research and practice: collaboration to improve care and outcomes for children and families.

PubMed

Kazak, Anne E; Noll, Robert B

2015-01-01

Childhood cancers are life-threatening diseases that are universally distressing and potentially traumatic for children and their families at diagnosis, during treatment, and beyond. Dramatic improvements in survival have occurred as a result of increasingly aggressive multimodal therapies delivered in the context of clinical research trials. Nonetheless, cancers remain a leading cause of death in children, and their treatments have short- and long-term impacts on health and well-being. For over 35 years, pediatric psychologists have partnered with pediatric oncology teams to make many contributions to our understanding of the impact of cancer and its treatment on children and families and have played prominent roles in providing an understanding of treatment-related late effects and in improving quality of life. After discussing the incidence of cancer in children, its causes, and the treatment approaches to it in pediatric oncology, we present seven key contributions of psychologists to collaborative and integrated care in pediatric cancer: managing procedural pain, nausea, and other symptoms; understanding and reducing neuropsychological effects; treating children in the context of their families and other systems (social ecology); applying a developmental perspective; identifying competence and vulnerability; integrating psychological knowledge into decision making and other clinical care issues; and facilitating the transition to palliative care and bereavement. We conclude with a discussion of the current status of integrating knowledge from psychological research into practice in pediatric cancer. PsycINFO Database Record (c) 2015 APA, all rights reserved.

The Exceptional Responders Initiative: Welcoming More Cases

Cancer.gov

The initiative is studying tissue, clinical, and genomic data from patients with cancer who have had dramatic and long-lasting responses to standard and experimental treatments that were not seen in similar patients who received the same treatment.

Cognitive and affective responses to lithium in patients with organic brain syndrome.

PubMed

Williams, K H; Goldstein, G

1979-06-01

The authors describe a series of patients with organic brain syndrome who showed a dramatic clinical response to lithium carbonate therapy. None of the patients had been diagnosed as manic-depressive. Most had extensive psychiatric treatment experiences and had been given both affective and cognitive diagnoses. Six of the eight patients also qualified for the diagnosis of alcoholism. They had been treated with a wide variety of psychotherapeutic medications. Lithium was found to be rapidly and dramatically effective in patients with static lesions of the central nervous system who showed a combination of dementia and agitated depression.

Rapidly Progressive Osteoarthritis: a Review of the Clinical and Radiologic Presentation.

PubMed

Flemming, Donald J; Gustas-French, Cristy N

2017-07-01

The purpose of this paper is to review the distinct clinical and radiographic features that may lead to prompt diagnosis of rapidly progressive osteoarthritis (RPOA) and thus obviate unnecessary and costly diagnostic workup. RPOA is uncommon but is more frequently seen in practice because of the aging population. RPOA is a destructive arthropathy that occurs most commonly in elderly women but can also be seen in patients that have sustained trauma. The dramatic radiologic manifestations of RPOA can lead to diagnostic confusion with other arthropathies, infection, and osteonecrosis. RPOA was originally described in the hip but may also involve the shoulder. The etiology of RPOA is not well understood, but subchondral fracture probably plays a role in the development of dramatic destruction of the joint that is seen in affected patients. Early diagnosis may reduce the complexity of surgical management. RPOA is an uncommon condition that occurs most frequently in elderly woman or in patients who have sustained trauma. Prompt recognition of the clinical and radiologic features of this arthropathy can reduce unnecessary diagnostic workup and complexity of surgical intervention.

Implementing Innovative Elementary Literacy Programs. Program Report.

ERIC Educational Resources Information Center

Schwab, R. G. Jerry; And Others

This four-document collection describes the implementation processes of dramatically improved literacy programs in elementary schools which are leading the move to restructure literacy education in the Northwest (Alaska, Idaho, Montana, Oregon, and Washington). The first document in the collection, "Strategies for Improving School-Wide…

Dramatic Improvements in Beach Water Quality Following Gull Removal

EPA Science Inventory

Gulls are often cited as important contributors of fecal contamination to surface waters, and some recreational beaches have used gull control measures to improve microbial water quality. In this study, gulls were chased from a Lake Michigan beach using specially trained dogs, a...

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

PubMed

Mazor, Roei D; Manevich-Mazor, Mirra; Kesler, Anat; Aizenstein, Orna; Eshed, Iris; Jaffe, Ronald; Pessach, Yakov; Goldberg, Ilan; Sprecher, Eli; Yaish, Iris; Gural, Alexander; Ganzel, Chezi; Shoenfeld, Yehuda

2014-12-01

Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

Big Data Application in Biomedical Research and Health Care: A Literature Review.

PubMed

Luo, Jake; Wu, Min; Gopukumar, Deepika; Zhao, Yiqing

2016-01-01

Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care.

Sustained improvements in plasma ACTH and clinical status in a patient with Nelson's syndrome treated with pasireotide LAR, a multireceptor somatostatin analog.

PubMed

Katznelson, Laurence

2013-05-01

Nelson's syndrome refers to aggressive pituitary corticotroph adenoma growth after bilateral adrenalectomy for treatment of Cushing's disease (CD). Pasireotide, a novel somatostatin analog, has been effective in treating CD. Here, the first case report of a patient with Nelson's syndrome treated with pasireotide is presented. A 55-year-old female was diagnosed with CD in 1973 at age 15 years and underwent bilateral adrenalectomy 1 year later. She subsequently developed Nelson's syndrome and underwent multiple surgeries and radiotherapy for adenoma growth. After presentation with ocular pain, third cranial nerve palsy, and a finding of suprasellar tumor enlargement with hemorrhage, she began pasireotide long-acting release 60 mg/28 days im. At baseline, fasting plasma ACTH was 42 710 pg/mL (normal, 5-27 pg/mL), and fasting plasma glucose was 98 mg/dL. After 1 month, ACTH declined to 4272 pg/mL, and it has remained stable over 19 months of follow-up. Hyperpigmentation progressively improved. Magnetic resonance imaging scans show reduction in the suprasellar component. Fasting plasma glucose increased to 124 mg/dL, and the patient underwent diabetes management. In this clinical case seminar, the current understanding of the treatment of Nelson's syndrome and the use of pasireotide in CD are summarized. A case of Nelson's syndrome with clinically significant and dramatic biochemical and clinical responses to pasireotide administration is reported. Hyperglycemia was noted after pasireotide administration. Pasireotide may represent a useful tool in the medical management of Nelson's syndrome. Further study of the potential benefits and risks of pasireotide in this population is necessary.

Big Data Application in Biomedical Research and Health Care: A Literature Review

PubMed Central

Luo, Jake; Wu, Min; Gopukumar, Deepika; Zhao, Yiqing

2016-01-01

Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care. PMID:26843812

Impact of a voice recognition system on report cycle time and radiologist reading time

NASA Astrophysics Data System (ADS)

Melson, David L.; Brophy, Robert; Blaine, G. James; Jost, R. Gilbert; Brink, Gary S.

1998-07-01

Because of its exciting potential to improve clinical service, as well as reduce costs, a voice recognition system for radiological dictation was recently installed at our institution. This system will be clinically successful if it dramatically reduces radiology report turnaround time without substantially affecting radiologist dictation and editing time. This report summarizes an observer study currently under way in which radiologist reporting times using the traditional transcription system and the voice recognition system are compared. Four radiologists are observed interpreting portable intensive care unit (ICU) chest examinations at a workstation in the chest reading area. Data are recorded with the radiologists using the transcription system and using the voice recognition system. The measurements distinguish between time spent performing clerical tasks and time spent actually dictating the report. Editing time and the number of corrections made are recorded. Additionally, statistics are gathered to assess the voice recognition system's impact on the report cycle time -- the time from report dictation to availability of an edited and finalized report -- and the length of reports.

Osimertinib in patients with advanced epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: rationale, evidence and place in therapy

PubMed Central

Ricciuti, Biagio; Baglivo, Sara; Paglialunga, Luca; De Giglio, Andrea; Bellezza, Guido; Chiari, Rita; Crinò, Lucio; Metro, Giulio

2017-01-01

The identification of epidermal growth factor receptor (EGFR) mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant EGFR through EGFR-tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit. Unfortunately, virtually all patients who initially respond to treatment develop acquired resistance to EGFR-TKIs within 9–14 months. The EGFR T790M secondary mutation has emerged as a cause of treatment failure in approximately 60% of resistant cases. To date, several compounds designed with the aim to overcome T790M-mediated resistance are under clinical investigation. The aim of this review is to discuss emerging data regarding the third-generation EGFR-TKI, osimertinib, for the treatment of EGFR T790M mutant advanced NSCLC. PMID:28607578

A case of idiopathic diabetes insipidus presented with bilateral hydroureteronephrosis and neurogenic bladder: A pediatric case report and literature review

PubMed Central

Yuksel, Ozgur Haki; Kivrak, Mithat; Sahin, Aytac; Akan, Serkan; Urkmez, Ahmet; Verit, Ayhan

2015-01-01

Diabetes insipidus (DI) is a condition with heterogeneous clinical symptoms characterized by polyuria (urine output >4 mL/kg/hr) and polydipsia (water intake >2 L/m 2/d). In children, acquired nephrogenic DI (NDI) is more common than central DI (CDI). Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. A water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI from CDI and diagnose their incomplete forms. Neonates and young infants are better managed with hydration therapy alone. Older children with CDI are treated with desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP). Its oral form is safe, highly effective and has dosing flexibility. We report a case of an 8-year-old male patient with CDI with severe bilateral non-obstructive hydronephrosis and megaureter. Dramatic clinical and radiological responses to dDAVP treatment were achieved and therapy reduced urine volume and led to marked radiological improvement in hydronephrosis. PMID:26600892

Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review

PubMed Central

Li, Yike; Garrett, Gaelyn; Zealear, David

2017-01-01

Vocal fold paralysis (VFP) refers to neurological causes of reduced or absent movement of one or both vocal folds. Bilateral VFP (BVFP) is characterized by inspiratory dyspnea due to narrowing of the airway at the glottic level with both vocal folds assuming a paramedian position. The primary objective of intervention for BVFP is to relieve patients’ dyspnea. Common clinical options for management include tracheostomy, arytenoidectomy and cordotomy. Other options that have been used with varying success include reinnervation techniques and botulinum toxin (Botox) injections into the vocal fold adductors. More recently, research has focused on neuromodulation, laryngeal pacing, gene therapy, and stem cell therapy. These newer approaches have the potential advantage of avoiding damage to the voicing mechanism of the larynx with an added goal of restoring some physiologic movement of the affected vocal folds. However, clinical data are scarce for these new treatment options (i.e., reinnervation and pacing), so more investigative work is needed. These areas of research are expected to provide dramatic improvements in the treatment of BVFP. PMID:28669149

Hepatitis A outbreak in Ba subdivision, Fiji, October-December 2013.

PubMed

Getahun, Aneley; Rafai, Eric; Tolosa, Maria Ximena; Dawainavesi, Akanisi; Tabua, Anaseini Maisema; Tabua, Josefa

2015-01-01

A cluster of suspected hepatitis A cases was notified to the Fiji Ministry of Health on 22 October 2013. An outbreak investigation team was mobilized to confirm the existence of an outbreak of hepatitis A and advise appropriate public health interventions. A case definition for the outbreak investigation was established, and standardized data collection tools were used to collect information on clinical presentation and risk factors. An environmental assessment was also conducted. There were 160 clinical cases of hepatitis A of which 15 were laboratory-confirmed. The attack rate was 349 per 10,000 population in the Nukuloa nursing zone; there were no reported deaths. Residents of the Nukuloa settlement were 6.6 times more likely to present with symptomatic hepatitis A infection (95% confidence interval: 3.8-12.6) compared with residents of another village with a different water supply. This is the first significant hepatitis A outbreak documented in Ba subdivision and possibly in Fiji. Enhanced surveillance of hepatitis A may reveal other clusters in the country. Improving the primary water source dramatically reduced the occurance of disease in the affected community and adjacent areas.

A case of idiopathic diabetes insipidus presented with bilateral hydroureteronephrosis and neurogenic bladder: A pediatric case report and literature review.

PubMed

Yuksel, Ozgur Haki; Kivrak, Mithat; Sahin, Aytac; Akan, Serkan; Urkmez, Ahmet; Verit, Ayhan

2015-01-01

Diabetes insipidus (DI) is a condition with heterogeneous clinical symptoms characterized by polyuria (urine output >4 mL/kg/hr) and polydipsia (water intake >2 L/m (2)/d). In children, acquired nephrogenic DI (NDI) is more common than central DI (CDI). Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. A water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI from CDI and diagnose their incomplete forms. Neonates and young infants are better managed with hydration therapy alone. Older children with CDI are treated with desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP). Its oral form is safe, highly effective and has dosing flexibility. We report a case of an 8-year-old male patient with CDI with severe bilateral non-obstructive hydronephrosis and megaureter. Dramatic clinical and radiological responses to dDAVP treatment were achieved and therapy reduced urine volume and led to marked radiological improvement in hydronephrosis.

Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa.

PubMed

Chi, Benjamin H; Stringer, Jeffrey S A; Moodley, Dhayendre

2013-06-01

Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges--and opportunities--of improving health services for HIV-infected mothers and their children across the region.

Treatment of inflammatory facial acne vulgaris in Chinese patients with the 1450-nm diode laser: a pilot study

NASA Astrophysics Data System (ADS)

Liu, Huaxu; Dang, Yongyan; Wang, Zhan; Ma, Li; Ren, Qiushi

2007-02-01

The 1450-nm diode laser has been found to be effective for the treatment of inflammatory acne in USA, Europe and Japan. However, there is no report on its efficacy in Chinese acne vulgaris patients. We conduct this pilot study to evaluate the efficacy and safety of the 1450-nm diode laser in the treatment of inflammatory facial acne vulgaris in Chinese patients. Nineteen patients with inflammatory facial acne were treated with the 1450-nm diode laser at 4- to 6-week intervals. Clinical photographs and lesion counts were obtained at baseline and after each treatment. Subjective evaluation of response to treatment and pain was assessed using a questionnaire. In our study, clinical improvement was seen in all patients and was generally dramatic. Lesion counts decreased 34% after one treatment (p<0.01), 56% after two treatments (p<0.01), and 81% after three treatments (p<0.01). However, the treatment-related pain was comparatively hard to be tolerated in Chinese patitents, and the other main adverse effect was the hyper-pigmentation after treatments (36.84%, 7/19).

A quality management systems approach for CD4 testing in resource-poor settings.

PubMed

Westerman, Larry E; Kohatsu, Luciana; Ortiz, Astrid; McClain, Bernice; Kaplan, Jonathan; Spira, Thomas; Marston, Barbara; Jani, Ilesh V; Nkengasong, John; Parsons, Linda M

2010-10-01

Quality assurance (QA) is a systematic process to monitor and improve clinical laboratory practices. The fundamental components of a laboratory QA program include providing a functional and safe laboratory environment, trained and competent personnel, maintained equipment, adequate supplies and reagents, testing of appropriate specimens, internal monitoring of quality, accurate reporting, and external quality assessments. These components are necessary to provide accurate and precise CD4 T-cell counts, an essential test to evaluate start of and monitor effectiveness of antiretroviral therapy for HIV-infected patients. In recent years, CD4 testing has expanded dramatically in resource-limited settings. Information on a CD4 QA program as described in this article will provide guidelines not only for clinical laboratory staff but also for managers of programs responsible for supporting CD4 testing. All agencies involved in implementing CD4 testing must understand the needs of the laboratory and provide advocacy, guidance, and financial support to established CD4 testing sites and programs. This article describes and explains the procedures that must be put in place to provide reliable CD4 determinations in a variety of settings.

[Medical errors: inevitable but preventable].

PubMed

Giard, R W

2001-10-27

Medical errors are increasingly reported in the lay press. Studies have shown dramatic error rates of 10 percent or even higher. From a methodological point of view, studying the frequency and causes of medical errors is far from simple. Clinical decisions on diagnostic or therapeutic interventions are always taken within a clinical context. Reviewing outcomes of interventions without taking into account both the intentions and the arguments for a particular action will limit the conclusions from a study on the rate and preventability of errors. The interpretation of the preventability of medical errors is fraught with difficulties and probably highly subjective. Blaming the doctor personally does not do justice to the actual situation and especially the organisational framework. Attention for and improvement of the organisational aspects of error are far more important then litigating the person. To err is and will remain human and if we want to reduce the incidence of faults we must be able to learn from our mistakes. That requires an open attitude towards medical mistakes, a continuous effort in their detection, a sound analysis and, where feasible, the institution of preventive measures.

Nucleic Acids for Ultra-Sensitive Protein Detection

PubMed Central

Janssen, Kris P. F.; Knez, Karel; Spasic, Dragana; Lammertyn, Jeroen

2013-01-01

Major advancements in molecular biology and clinical diagnostics cannot be brought about strictly through the use of genomics based methods. Improved methods for protein detection and proteomic screening are an absolute necessity to complement to wealth of information offered by novel, high-throughput sequencing technologies. Only then will it be possible to advance insights into clinical processes and to characterize the importance of specific protein biomarkers for disease detection or the realization of “personalized medicine”. Currently however, large-scale proteomic information is still not as easily obtained as its genomic counterpart, mainly because traditional antibody-based technologies struggle to meet the stringent sensitivity and throughput requirements that are required whereas mass-spectrometry based methods might be burdened by significant costs involved. However, recent years have seen the development of new biodetection strategies linking nucleic acids with existing antibody technology or replacing antibodies with oligonucleotide recognition elements altogether. These advancements have unlocked many new strategies to lower detection limits and dramatically increase throughput of protein detection assays. In this review, an overview of these new strategies will be given. PMID:23337338

Primary focal hyperhidrosis: diagnosis and management. .

PubMed

Wang, Rena; Solish, Nowell; Murray, Christian A

2008-12-01

Primary focal hyperhidrosis is a common and serious medical condition that causes considerable psychosocial morbidity. Diagnostic and effective management strategies can improve patients' quality of living dramatically.

Non-Traditional Methods of Improving the Communication Skills of Disadvantaged Students

ERIC Educational Resources Information Center

Wilson, Brenda M.; Power, Marian E.

1978-01-01

Educators are encouraged to use some of the non-traditional student-centered methods for improving the communication skills of disadvantaged students, including technological aids such as books, tapes, cable T.V., video tapes, computers, etc., and devices such as role playing and dramatizations. (AM)

Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

PubMed

Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J

2017-11-15

Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Aspergillus vertebral osteomyelitis in a child with a primary monocyte killing defect: response to GM-CSF therapy.

PubMed

Abu Jawdeh, L; Haidar, R; Bitar, F; Mroueh, S; Akel, S; Nuwayri-Salti, N; Dbaibo, G S

2000-07-01

We report the first case of vertebral aspergillosis in a child with a primary defect in monocyte killing, an extremely rare immunodeficiency The diagnosis of defective monocyte killing was made by an in vitro assay that showed normal killing of Staphylococcus aureus by the patient's neutrophils but impaired killing by his monocytes. Importantly, the extensive granulomatous infection that involved the vertebral column, posterior mediastinum, pleura, and lung was not responsive to aggressive treatment with a combination of liposomal amphotericin B. intralesional amphotericin B. itraconazole, and granulocyte transfusions. Dramatic clinical and radiological improvement was only seen after the addition of granulocyte macrophage-colony stimulating factor (GM-CSF) to his treatment regimen. The use of GM-CSF in the treatment of invasive aspergillosis in immunocompromised patients requires further evaluation.

The High-Throughput Analyses Era: Are We Ready for the Data Struggle?

PubMed

D'Argenio, Valeria

2018-03-02

Recent and rapid technological advances in molecular sciences have dramatically increased the ability to carry out high-throughput studies characterized by big data production. This, in turn, led to the consequent negative effect of highlighting the presence of a gap between data yield and their analysis. Indeed, big data management is becoming an increasingly important aspect of many fields of molecular research including the study of human diseases. Now, the challenge is to identify, within the huge amount of data obtained, that which is of clinical relevance. In this context, issues related to data interpretation, sharing and storage need to be assessed and standardized. Once this is achieved, the integration of data from different -omic approaches will improve the diagnosis, monitoring and therapy of diseases by allowing the identification of novel, potentially actionably biomarkers in view of personalized medicine.

Radionuclide Imaging of Neurohormonal System of the Heart

PubMed Central

Chen, Xinyu; Werner, Rudolf A.; Javadi, Mehrbod S.; Maya, Yoshifumi; Decker, Michael; Lapa, Constantin; Herrmann, Ken; Higuchi, Takahiro

2015-01-01

Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included. PMID:25825596

Beyond fast food and slow motion: Weighty contributors to the obesity epidemic

PubMed Central

Cizza, G.; Rother, K.I.

2012-01-01

Decreased physical activity and marketing-driven increased consumption of “junk” food, dubbed “The Big Two”, are generally regarded as the most important contributors to the obesity epidemic. However, the full picture contains many more pieces of the puzzle. We address several additional issues and review current clinical developments in obesity research. In spite of dramatic advancements in our understanding of the adipose organ and its endocrine and immune products, the ultimate causes of the obesity epidemic remain elusive. Treatment is plagued by poor adherence to life style modifications, and available pharmacological options are marginally effective, often also associated with major side effects. Surgical treatments, albeit effective in decreasing body weight, are invasive and expensive. Thus, our approaches to finding the causes, improving the existing treatments, and inventing novel therapies must be manifold. PMID:22183119

Rare case of left-dominant arrhythmogenic right ventricular cardiomyopathy with dramatic reverse remodeling after cardiac resynchronization as an adjunct to pharmacological therapy.

PubMed

Hsiao, Chih-Chung; Kuo, Jen-Yuan; Yun, Chun-Ho; Hung, Chung-Lieh; Tsai, Cheng-Ho; Yeh, Hung-I

2012-01-01

A 57-year-old man presented with near syncope and hemodynamic compromise after exercise. A sustained ventricular tachycardia (VT) of right bundle-branch block morphology was evident upon examination at our emergency department. Baseline 12-lead electrocardiography revealed a sinus rhythm with a complete left bundle-branch block after successful cardioversion of the VT. Coronary angiography revealed patent coronary arteries, whereas left ventriculography demonstrated impaired systolic function, accompanied by a peculiar basal lateral aneurysm. Both echocardiography and magnetic resonance imaging were consistent with a diagnosis of left-dominant arrhythmogenic right ventricular cardiomyopathy. Four months later, substantial ventricular reverse remodeling and clinical improvements were observed after cardiac resynchronization therapy with a defibrillator, as an adjunct to conventional pharmacological therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Beyond fast food and slow motion: weighty contributors to the obesity epidemic.

PubMed

Cizza, G; Rother, K I

2012-02-01

Decreased physical activity and marketing-driven increased consumption of "junk" food, dubbed "The Big Two", are generally regarded as the most important contributors to the obesity epidemic. However, the full picture contains many more pieces of the puzzle. We address several additional issues and review current clinical developments in obesity research. In spite of dramatic advancements in our understanding of the adipose organ and its endocrine and immune products, the ultimate causes of the obesity epidemic remain elusive. Treatment is plagued by poor adherence to life style modifications, and available pharmacological options are marginally effective, often also associated with major side effects. Surgical treatments, albeit effective in decreasing body weight, are invasive and expensive. Thus, our approaches to finding the causes, improving the existing treatments, and inventing novel therapies must be manifold.

A life-threatening case of TAFRO syndrome with dramatic response to tocilizumab, rituximab, and pulse steroids: The first case report in Latin America.

PubMed

José, Fabio Freire; Kerbauy, Lucila Nassif; Perini, Guilherme Fleury; Blumenschein, Danielle Isadora; Pasqualin, Denise da Cunha; Malheiros, Denise Maria Avancini Costa; Campos Neto, Guilherme de Carvalho; de Souza Santos, Fabio Pires; Piovesan, Ronaldo; Hamerschlak, Nelson

2017-03-01

This is the report of the first case of TAFRO syndrome (Thrombocytopenia, Anasarca, myelofibrosis, Renal dysfunction, Organomegaly) in Latin America. The patient was a 61-year-old white woman of Ashkenazi Jewish descent, who presented with a history of 8 days of nausea, vomiting, and fever; severe pitting edema in both legs, ascites, splenomegaly, and palpable axillary lymph nodes. Abdominal computed tomography (CT) showed bilateral pleural effusion and retroperitoneal lymph node enlargement. Anasarca and worsening of renal function led to admission to the intensive care unit (ICU) with multiple organ failure, requiring mechanical ventilation, vasopressor medications, and continuous renal replacement therapy (CRRT). Diagnosis of TAFRO syndrome was made on day 18 after admission, based on clinical findings and results of bone marrow and lymph node biopsies. She was treated with methylprednisolone, tocilizumab, and rituximab. One week after the first tocilizumab dose, she had dramatic improvements in respiratory and hemodynamic status, and was weaned from ventilator support and vasopressor medications. After 2 weeks of therapy, CRRT was switched to intermittent hemodialysis. On day 46, the patient was discharged from the ICU to the general ward, and 3 months after admission, she went home. Provided the interleukin-6 measurement is available, this approach is suggested in cases of TAFRO syndrome, in order to customize the treatment.

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

2012-02-01

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

Exceptional Children Conference Papers: Gifted and Talented.

ERIC Educational Resources Information Center

Council for Exceptional Children, Arlington, VA.

Educators concerned with improving educational opportunities for the gifted need to consider ways to achieve their ends within the realities of the political system. Federal programs cannot be expected to provide ideas which will dramatically improve education for the gifted nor to provide large quantities of money. The federal government can…

Using JournalMap to improve discovery and visualization of rangeland scientific knowledge

USDA-ARS?s Scientific Manuscript database

Most of the ecological research conducted around the world is tied to specific places; however, that location information is locked up in the text and figures of scientific articles in myriad forms that are not easily searchable. While access to ecological literature has improved dramatically in the...

School Turnaround Fever: The Paradoxes of a Historical Practice Promoted as a New Reform

ERIC Educational Resources Information Center

Peck, Craig; Reitzug, Ulrich C.

2014-01-01

School "turnaround" has received significant attention recently in education literature and policy action, especially as a means to dramatically improve urban education. In current common education usage, "turnaround" refers to the rapid, significant improvement in the academic achievement of persistently low-achieving schools.…

Clinical applications of commercially available video recording and monitoring systems: inexpensive, high-quality video recording and monitoring systems for endoscopy and microsurgery.

PubMed

Tsunoda, Koichi; Tsunoda, Atsunobu; Ishimoto, ShinnIchi; Kimura, Satoko

2006-01-01

The exclusive charge-coupled device (CCD) camera system for the endoscope and electronic fiberscopes are in widespread use. However, both are usually stationary in an office or examination room, and a wheeled cart is needed for mobility. The total costs of the CCD camera system and electronic fiberscopy system are at least US Dollars 10,000 and US Dollars 30,000, respectively. Recently, the performance of audio and visual instruments has improved dramatically, with a concomitant reduction in their cost. Commercially available CCD video cameras with small monitors have become common. They provide excellent image quality and are much smaller and less expensive than previous models. The authors have developed adaptors for the popular mini-digital video (mini-DV) camera. The camera also provides video and acoustic output signals; therefore, the endoscopic images can be viewed on a large monitor simultaneously. The new system (a mini-DV video camera and an adaptor) costs only US Dollars 1,000. Therefore, the system is both cost-effective and useful for the outpatient clinic or casualty setting, or on house calls for the purpose of patient education. In the future, the authors plan to introduce the clinical application of a high-vision camera and an infrared camera as medical instruments for clinical and research situations.

Automation in Clinical Microbiology

PubMed Central

Ledeboer, Nathan A.

2013-01-01

Historically, the trend toward automation in clinical pathology laboratories has largely bypassed the clinical microbiology laboratory. In this article, we review the historical impediments to automation in the microbiology laboratory and offer insight into the reasons why we believe that we are on the cusp of a dramatic change that will sweep a wave of automation into clinical microbiology laboratories. We review the currently available specimen-processing instruments as well as the total laboratory automation solutions. Lastly, we outline the types of studies that will need to be performed to fully assess the benefits of automation in microbiology laboratories. PMID:23515547

The Growth of Retail Clinics and the Medical Home: Two Trends in Conflict?

PubMed Central

Pollack, Craig Evan; Gidengil, Courtney; Mehrotra, Ateev

2012-01-01

There has been growing interest in the patient-centered medical home as a way to provide coordinated, high quality primary care. At the same time the number of retail clinics has increased dramatically. Many are concerned that retail clinics undermine the medical home by fragmenting care. In this piece we explore the juxtaposition of these trends, highlighting shared characteristics and sources of tension. We describe three types of relationships between retail clinics and primary care providers. With some relationships we argue that there is no conflict, while we describe areas of potential concern for other relationships. PMID:20439897

Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer1

PubMed Central

Kurhanewicz, John; Vigneron, Daniel B; Nelson, Sarah J

2000-01-01

Abstract Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy. PMID:10933075

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

PubMed

Leather, A T; Studd, J W; Watson, N R; Holland, E F

1999-02-01

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases.

PubMed

Bonney, Phillip A; Santucci, Joshua A; Maurer, Adrian J; Sughrue, Michael E; McNall-Knapp, Rene Y; Battiste, James D

2016-04-01

There is little evidence to guide the choice of chemotherapeutic agents for osseous metastases in medulloblastoma. Recently, triple therapy with temozolomide, irinotecan, and bevacizumab has been reported to have efficacy in recurrent medulloblastoma, and this regimen alone and in combination with other agents has been tested in several early-phase clinical trials. Here we report a 20-year-old woman with multiply-relapsed medulloblastoma with numerous osseous metastases 8 years after original diagnosis who responded dramatically to temozolomide, irinotecan, and bevacizumab therapy. This case highlights the potential for this regimen in treating osseous metastases in medulloblastoma. Copyright © 2016. Published by Elsevier Ltd.

Fusion maldevelopment (latent/manifest latent) nystagmus syndrome: effects of four-muscle tenotomy and reattachment.

PubMed

Dell'Osso, Louis F; Orge, Faruk H; Jacobs, Jonathan B; Wang, Zhong I

2014-01-01

To examine the waveform and clinical effects of the four-muscle tenotomy and reattachment procedure in fusion maldevelopment nystagmus syndrome (FMNS) and to compare them to those documented in infantile nystagmus syndrome (INS) and acquired nystagmus. Both infrared reflection and high-speed digital video systems were used to record the eye movements in a patient with FMNS (before and after tenotomy and reattachment). Data were analyzed using the eXpanded Nystagmus Acuity Function (NAFX) that is part of the OMtools software. Model simulations and predictions were performed using the authors' behavioral ocular motor system model in MATLAB Simulink (The MathWorks, Inc., Natick, MA). The model predicted, and the patient's data confirmed, that the tenotomy and reattachment procedure produces improvements in FMN waveforms across a broader field of gaze and decreases the Alexander's law variation. The patient's tenotomy and reattachment plots of NAFX after surgery versus gaze angle were higher and had lower slope than before surgery. Clinically, despite moderate improvements in both peak measured acuity and stereoacuity, dramatic improvements in the patient's abilities and lifestyle resulted. The four-muscle tenotomy and reattachment nystagmus surgery produced beneficial therapeutic effects on FMN waveforms that are similar to those demonstrated in INS and acquired nystagmus. These results support the authors' prior recommendation that tenotomy and reattachment nystagmus should be added to required strabismus procedures in patients who also have FMNS (ie, perform tenotomy and reattachment on all unoperated muscles in the plane of the nystagmus). Furthermore, when strabismus surgery is not required, four-muscle tenotomy and reattachment may be used to improve FMN waveforms and visual function. Copyright 2014, SLACK Incorporated.

Systemic amyloidosis: novel therapies and role of biomarkers.

PubMed

Nuvolone, Mario; Merlini, Giampaolo

2017-05-01

Systemic amyloidosis is caused by misfolding and extracellular deposition of one of an ever-growing list of circulating proteins, resulting in vital organ dysfunction and eventually death. Despite different predisposing conditions, including plasma cell dyscrasias [immunoglobulin light chain (AL) amyloidosis], long-lasting inflammation [reactive (AA) amyloidosis] or mutations (hereditary amyloidoses), clinical manifestations are conspicuously overlapping and mimic more prevalent conditions, significantly complicating and often delaying the recognition of these rare, complex diseases. However, refined diagnostic and imaging approaches and the increasing role of biomarkers, which help in establishing the diagnosis, assessing the prognosis and evaluating the response to therapy, have considerably improved the management of these conditions. The pillar of anti-amyloid therapy remains the prompt reduction or elimination of the amyloidogenic precursor. This is accomplished by targeting the underlying condition, and recent improvements in the treatment of plasma cell disorders and chronic inflammatory conditions have positively reverberated onto the management of AL and AA amyloidosis, respectively. Moreover, recent, substantial improvements in the understanding of the molecular underpinnings of systemic amyloidosis have unveiled different key steps in the amyloidogenic cascade which can be valid therapeutic targets. These include stabilizers of the native conformation of the amyloidogenic precursor, inhibitors of fibrillogenesis, amyloid fibril disruptors and promoters of amyloid clearance. Innovative pharmacological strategies, including rational, structure-based drug design, gene knockdown and immunotherapy, but also repurposing of old, safe drugs with newly recognized anti-amyloid properties, are currently being pursued already in the clinical setting, holding the promise of dramatically improving the outcome of these dismal conditions in the near future. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Optimized Lentiviral Vector Design Improves Titer and Transgene Expression of Vectors Containing the Chicken β-Globin Locus HS4 Insulator Element

PubMed Central

Hanawa, Hideki; Yamamoto, Motoko; Zhao, Huifen; Shimada, Takashi; Persons, Derek A

2009-01-01

Hematopoietic cell gene therapy using retroviral vectors has achieved success in clinical trials. However, safety issues regarding vector insertional mutagenesis have emerged. In two different trials, vector insertion resulted in the transcriptional activation of proto-oncogenes. One strategy for potentially diminishing vector insertional mutagenesis is through the use of self-inactivating lentiviral vectors containing the 1.2-kb insulator element derived from the chicken β-globin locus. However, use of this element can dramatically decrease both vector titer and transgene expression, thereby compromising its practical use. Here, we studied lentiviral vectors containing either the full-length 1.2-kb insulator or the smaller 0.25-kb core element in both orientations in the partially deleted long-terminal repeat. We show that use of the 0.25-kb core insulator rescued vector titer by alleviating a postentry block to reverse transcription associated with the 1.2-kb element. In addition, in an orientation-dependent manner, the 0.25-kb core element significantly increased transgene expression from an internal promoter due to improved transcriptional termination. This element also demonstrated barrier activity, reducing variability of expression due to position effects. As it is known that the 0.25-kb core insulator has enhancer-blocking activity, this particular insulated lentiviral vector design may be useful for clinical application. PMID:19223867

Economic burden of psoriatic patients in Japan: Analysis from a single outpatient clinic.

PubMed

Takahashi, Hidetoshi; Satoh, Katsuhiko; Takagi, Akiyoshi; Iizuka, Hajime

2017-09-01

Topical and systemic agents have dramatically improved the treatment efficacy of psoriasis. Few reports, however, exist describing the economic burden in Japanese psoriatic patients. The aim of the study was to evaluate the total costs as well as cost versus efficacy of topical and systemic treatments of psoriatic patients under the Japanese health insurance system. The retrospective study was performed from the database of our clinic, which is located in Hokkaido Prefecture. Cost and effectiveness of psoriatic patients were evaluated during the 12-month period from April 2015 to March 2016. Data were collected and calculated for the total cost per year, treatment efficacy and cost versus efficacy. The mean total cost of topical corticosteroid treatment was ¥18 184/year and was lowest among the treatments. The systemic treatment with biologics was most expensive and the costs were over ¥400 000/year. Among the topical treatments, calcipotriol/betamethasone dipropionate was most expensive (¥34 693/year). However, cost versus efficacy was not significantly different from that of topical corticosteroid treatments. The cost of secukinumab was highest among all the treatments (¥631 600/year). However, treatment day per cost was lowest of all the psoriasis treatments. Biologics showed the highest cost than topical or systemic treatments. However, they showed most marked efficacy in terms of improving the psoriatic skin lesions. © 2017 Japanese Dermatological Association.

Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

PubMed

Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

2016-06-13

The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

Sex Differences in Device Therapy for Heart Failure: Utilization, Outcomes, and Adverse Events

PubMed Central

Herz, Naomi D.; Engeda, Joseph; Zusterzeel, Robbert; Sanders, William E.; O'Callaghan, Kathryn M.; Strauss, David G.; Jacobs, Samantha B.; Selzman, Kimberly A.; Piña, Ileana L.

2015-01-01

Abstract Background: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. Methods: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. Results: Ninety percent of the studies evaluated included ≤35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. Conclusions: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex. PMID:25793483

Dosimetric Improvements with a Novel Breast Stereotactic Radiotherapy Device for Delivery of Preoperative Partial-Breast Irradiation.

PubMed

Snider, James W; Mutaf, Yildirim; Nichols, Elizabeth; Hall, Andrea; Vadnais, Patrick; Regine, William F; Feigenberg, Steven J

2017-01-01

Partial-breast irradiation (PBI) with external-beam radiotherapy has produced higher than expected rates of fair-to-poor cosmesis. Worsened outcomes have been correlated with larger volumes of breast tissue exposed to radiation. A novel breast-specific stereotactic radiotherapy (BSRT) device (BSRTD) has been developed at our institution and has shown promise in delivering highly conformal dose distributions. We compared normal tissue sparing with this device with that achieved with intensity-modulated radiation therapy (IMRT)-PBI. Fifteen women previously treated with breast conservation therapy were enrolled on an institutional review board-approved protocol. Each of them underwent CT simulation in the prone position using the BSRTD-specific immobilization system. Simulated postoperative and preoperative treatment volumes were generated based on surgical bed/clip position. Blinded planners generated IMRT-PBI plans and BSRT plans for each set of volumes. These plans were compared based on clinically validated markers for cosmetic outcome and toxicity using a Wilcoxon rank-sum test. The BSRT plans consistently reduced the volumes receiving each of several dose levels (Vx) to breast tissue, the chest wall, the lung, the heart, and the skin in both preoperative and postoperative settings (p < 0.05). Preoperative BSRT yielded particularly dramatic improvements. The novel BSRTD has demonstrated significant dosimetric benefits over IMRT-PBI. Further investigation is currently proceeding through initial clinical trials. © 2016 S. Karger AG, Basel.

Patient access in plastic surgery: an operational and financial analysis of service-based interventions to improve ambulatory throughput in an academic surgery practice.

PubMed

Hultman, Charles Scott; Gilland, Wendell G; Weir, Samuel

2015-06-01

Inefficient patient throughput in a surgery practice can result in extended new patient backlogs, excessively long cycle times in the outpatient clinics, poor patient satisfaction, decreased physician productivity, and loss of potential revenue. This project assesses the efficacy of multiple throughput interventions in an academic, plastic surgery practice at a public university. We implemented a Patient Access and Efficiency (PAcE) initiative, funded and sponsored by our health care system, to improve patient throughput in the outpatient surgery clinic. Interventions included: (1) creation of a multidisciplinary team, led by a project redesign manager, that met weekly; (2) definition of goals, metrics, and target outcomes; 3) revision of clinic templates to reflect actual demand; 4) working down patient backlog through group visits; 5) booking new patients across entire practice; 6) assigning a physician's assistant to the preoperative clinic; and 7) designating a central scheduler to coordinate flow of information. Main outcome measures included: patient satisfaction using Press-Ganey surveys; complaints reported to patient relations; time to third available appointment; size of patient backlog; monthly clinic volumes with utilization rates and supply/demand curves; "chaos" rate (cancellations plus reschedules, divided by supply, within 48 hours of booked clinic date); patient cycle times with bottleneck analysis; physician productivity measured by work Relative Value Units (wRVUs); and downstream financial effects on billing, collection, accounts receivable (A/R), and payer mix. We collected, managed, and analyzed the data prospectively, comparing the pre-PAcE period (6 months) with the PAcE period (6 months). The PAcE initiative resulted in multiple improvements across the entire plastic surgery practice. Patient satisfaction increased only slightly from 88.5% to 90.0%, but the quarterly number of complaints notably declined from 17 to 9. Time to third available new patient appointment dropped from 52 to 38 days, whereas the same metric for a preoperative appointment plunged from 46 to 16 days. The size of the new patient backlog fell from 169 to 110 patients, and total monthly clinic volume climbed from 574 to 766 patients. Our "chaos" rate dropped from 12.3% to 1.8%. Mean patient cycle time in the clinic decreased dramatically from 127 to 44 minutes. Mean monthly productivity for the practice increased from 2479 to 2702 RVUs. Although our collection rate did not change, days in A/R dropped from 66 to 57 days. Mean monthly charges increased from U.S. $535,213 to U.S. $583,193, and mean monthly collections improved from U.S. $181,967 to U.S. $210,987. Payer mix remained unchanged. Implementation of a PAcE initiative, focusing on outpatient clinic throughput, yields significant improvements in access to care, patient satisfaction as measured by complaints, physician productivity, and financial performance. An academic, university-based, plastic surgery practice can use throughput interventions to deliver timely care and to enhance financial viability.

Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

PubMed Central

Miras, A D; le Roux, C W

2014-01-01

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals. PMID:24213310

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

PubMed

Imbimbo, Martina; Maury, Jean-Michel; Garassino, Marina; Girard, Nicolas

2018-02-02

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Rhabdomyolysis in a Patient with Severe Hypothyroidism

PubMed Central

Salehi, Nooshin; Agoston, Endre; Munir, Iqbal; Thompson, Gary J.

2017-01-01

Patient: Female, 52 Final Diagnosis: Hypothyroidism induced rhabdomyolysis Symptoms: Bilateral leg pain • fatigue Medication: Levothyroxine • Calcitriol • Calcium Gluconate Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Muscular symptoms, including stiffness, myalgia, cramps, and fatigue, are present in the majority of the patients with symptomatic hypothyroidism, but rhabdomyolysis, the rapid breakdown of skeletal muscle, is a rare manifestation. In most patients with hypothyroidism who develop rhabdomyolysis, precipitating factors, such as strenuous exercise or use of lipid-lowering drugs, can be identified. Case Report: We report a case of a 52-year-old Hispanic woman with a history of hypothyroidism, hypertension, and type 2 diabetes mellitus who presented with fatigue, severe generalized weakness, bilateral leg pain, and recurrent falls. She reported poor medication compliance for the preceding month. Initial laboratory testing showed elevated thyroid stimulating hormone (TSH) and creatine kinase (CK) levels, indicating uncontrolled hypothyroidism with associated rhabdomyolysis. Supportive treatment with intravenous fluids and intravenous levothyroxine were initiated and resulted in dramatic clinical improvement. Conclusions: We report a case of rhabdomyolysis, which is a rare but potentially serious complication of hypothyroidism. Screening for hypothyroidism in patients with elevated muscle enzymes should be considered, since an early diagnosis and prompt treatment of hypothyroidism is essential to prevent rhabdomyolysis and its consequences. PMID:28827517

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

PubMed Central

Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

2016-01-01

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

Mobile devices for the remote acquisition of physiological and behavioral biomarkers in psychiatric clinical research.

PubMed

W Adams, Zachary; McClure, Erin A; Gray, Kevin M; Danielson, Carla Kmett; Treiber, Frank A; Ruggiero, Kenneth J

2017-02-01

Psychiatric disorders are linked to a variety of biological, psychological, and contextual causes and consequences. Laboratory studies have elucidated the importance of several key physiological and behavioral biomarkers in the study of psychiatric disorders, but much less is known about the role of these biomarkers in naturalistic settings. These gaps are largely driven by methodological barriers to assessing biomarker data rapidly, reliably, and frequently outside the clinic or laboratory. Mobile health (mHealth) tools offer new opportunities to study relevant biomarkers in concert with other types of data (e.g., self-reports, global positioning system data). This review provides an overview on the state of this emerging field and describes examples from the literature where mHealth tools have been used to measure a wide array of biomarkers in the context of psychiatric functioning (e.g., psychological stress, anxiety, autism, substance use). We also outline advantages and special considerations for incorporating mHealth tools for remote biomarker measurement into studies of psychiatric illness and treatment and identify several specific opportunities for expanding this promising methodology. Integrating mHealth tools into this area may dramatically improve psychiatric science and facilitate highly personalized clinical care of psychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intraindividual variation in core microbiota in peri-implantitis and periodontitis

PubMed Central

Maruyama, Noriko; Maruyama, Fumito; Takeuchi, Yasuo; Aikawa, Chihiro; Izumi, Yuichi; Nakagawa, Ichiro

2014-01-01

The oral microbiota change dramatically with each part of the oral cavity, even within the same mouth. Nevertheless, the microbiota associated with peri-implantitis and periodontitis have been considered the same. To improve our knowledge of the different communities of complex oral microbiota, we compared the microbial features between peri-implantitis and periodontitis in 20 patients with both diseases. Although the clinical symptoms of peri-implantitis were similar to those of periodontitis, the core microbiota of the diseases differed. Correlation analysis revealed the specific microbial co-occurrence patterns and found some of the species were associated with the clinical parameters in a disease-specific manner. The proportion of Prevotella nigrescens was significantly higher in peri-implantitis than in periodontitis, while the proportions of Peptostreptococcaceae sp. and Desulfomicrobium orale were significantly higher in periodontitis than in peri-implantitis. The severity of the peri-implantitis was also species-associated, including with an uncultured Treponema sp. that correlated to 4 clinical parameters. These results indicate that peri-implantitis and periodontitis are both polymicrobial infections with different causative pathogens. Our study provides a framework for the ecologically different bacterial communities between peri-implantitis and periodontitis, and it will be useful for further studies to understand the complex microbiota and pathogenic mechanisms of oral polymicrobial diseases. PMID:25308100

Big data in health care: using analytics to identify and manage high-risk and high-cost patients.

PubMed

Bates, David W; Saria, Suchi; Ohno-Machado, Lucila; Shah, Anand; Escobar, Gabriel

2014-07-01

The US health care system is rapidly adopting electronic health records, which will dramatically increase the quantity of clinical data that are available electronically. Simultaneously, rapid progress has been made in clinical analytics--techniques for analyzing large quantities of data and gleaning new insights from that analysis--which is part of what is known as big data. As a result, there are unprecedented opportunities to use big data to reduce the costs of health care in the United States. We present six use cases--that is, key examples--where some of the clearest opportunities exist to reduce costs through the use of big data: high-cost patients, readmissions, triage, decompensation (when a patient's condition worsens), adverse events, and treatment optimization for diseases affecting multiple organ systems. We discuss the types of insights that are likely to emerge from clinical analytics, the types of data needed to obtain such insights, and the infrastructure--analytics, algorithms, registries, assessment scores, monitoring devices, and so forth--that organizations will need to perform the necessary analyses and to implement changes that will improve care while reducing costs. Our findings have policy implications for regulatory oversight, ways to address privacy concerns, and the support of research on analytics. Project HOPE—The People-to-People Health Foundation, Inc.

A proteomic approach to obesity and type 2 diabetes.

PubMed

López-Villar, Elena; Martos-Moreno, Gabriel Á; Chowen, Julie A; Okada, Shigeru; Kopchick, John J; Argente, Jesús

2015-07-01

The incidence of obesity and type diabetes 2 has increased dramatically resulting in an increased interest in its biomedical relevance. However, the mechanisms that trigger the development of diabetes type 2 in obese patients remain largely unknown. Scientific, clinical and pharmaceutical communities are dedicating vast resources to unravel this issue by applying different omics tools. During the last decade, the advances in proteomic approaches and the Human Proteome Organization have opened and are opening a new door that may be helpful in the identification of patients at risk and to improve current therapies. Here, we briefly review some of the advances in our understanding of type 2 diabetes that have occurred through the application of proteomics. We also review, in detail, the current improvements in proteomic methodologies and new strategies that could be employed to further advance our understanding of this pathology. By applying these new proteomic advances, novel therapeutic and/or diagnostic protein targets will be discovered in the obesity/Type 2 diabetes area. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Malignancies in HIV-Infected and AIDS Patients.

PubMed

Ji, Yongjia; Lu, Hongzhou

2017-01-01

Currently, HIV infection and AIDS are still one of the most important epidemic diseases around the world. As early in the initial stage of HIV epidemic, the high incidence of ADCs including Kaposi sarcoma and non-Hodgkin's lymphoma was the substantial amount of disease burden of HIV infection and AIDS. With the increasing accessibility of HAART and improving medical care for HIV infection and AIDS, AIDS-related illness including ADCs has dramatically decreased. Meanwhile, the incidence of NADCs rises in PLWH. Compared with the general population, most of cancers are more likely to attack PLWH, and NADCs in PLWH were characterized as earlier onset and more aggressive. However, the understanding for cancer development in PLWH is still dimness. Herein, we reviewed the current knowledge of epidemiology and pathogenesis for malignancies in PLWH summarized from recent studies. On the basis of that, we discussed the special considerations for cancer treatment in PLWH. As those malignancies could be the major issue for HIV infection or AIDS in the future, we expect enhanced investigations, surveillances, and clinical trial for improving the understanding and management for cancers developed in PLWH.

A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men.

PubMed

Cases, Julien; Romain, Cindy; Dallas, Constantin; Gerbi, Alain; Rouanet, Jean Max

2015-01-01

Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

Clinical roundtable monograph: Unmet needs in the management of chronic myelogenous leukemia.

PubMed

Jabbour, Elias J; Bixby, Dale; Akard, Luke P

2012-12-01

Approximately 5,000 cases of chronic myelogenous leukemia (CML) are diagnosed each year in the United States. The introduction of tyrosine kinase inhibitors (TKIs) has dramatically improved survival time for many CML patients. Current first-line treatment options include imatinib and the second-generation agents nilotinib and dasatinib. Second- and third-line agents include nilotinib, dasatinib, bosutinib, and the new agent ponatinib. Despite the effectiveness of TKIs, some patients develop resistance or intolerance to these agents. A number of mutations of the BCR-ABL gene have been identified and are associated with TKI resistance. Patients may benefit from switching to a second-line TKI, undergoing hematopoietic stem cell transplant, or receiving newly emerging agents. Although early response is associated with improved patient outcome, clinicians lack tests that can determine which patients will benefit from which therapies. To ensure adequate response, patients should be monitored by both polymerase chain reaction and cytogenetic analysis of the bone marrow. This roundtable monograph reviews key unmet needs in patients with CML related to disease management and treatment options.

An Update on Aerosolized Antibiotics for Treating Hospital-Acquired and Ventilator-Associated Pneumonia in Adults.

PubMed

Wood, G Christopher; Swanson, Joseph M

2017-12-01

A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.

Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

PubMed

Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

2012-06-01

Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

Using screen-based simulation of inhaled anaesthetic delivery to improve patient care.

PubMed

Philip, J H

2015-12-01

Screen-based simulation can improve patient care by giving novices and experienced clinicians insight into drug behaviour. Gas Man(®) is a screen-based simulation program that depicts pictorially and graphically the anaesthetic gas and vapour tension from the vaporizer to the site of action, namely the brain and spinal cord. The gases and vapours depicted are desflurane, enflurane, ether, halothane, isoflurane, nitrogen, nitrous oxide, sevoflurane, and xenon. Multiple agents can be administered simultaneously or individually and the results shown on an overlay graph. Practice exercises provide in-depth knowledge of the subject matter. Experienced clinicians can simulate anaesthesia occurrences and practices for application to their clinical practice, and publish the results to benefit others to improve patient care. Published studies using this screen-based simulation have led to a number of findings, as follows: changing from isoflurane to desflurane toward the end of anaesthesia does not accelerate recovery in humans; vital capacity induction can produce loss of consciousness in 45 s; simulated context-sensitive decrement times explain recovery profiles; hyperventilation does not dramatically speed emergence; high fresh gas flow is wasteful; fresh gas flow and not the vaporizer setting should be reduced during intubation; re-anaesthetization can occur with severe hypoventilation after extubation; and in re-anaesthetization, the anaesthetic redistributes from skeletal muscle. Researchers using screen-based simulations can study fewer subjects to reach valid conclusions that impact clinical care. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Turning the tide against cancer through sustained medical innovation: the pathway to progress.

PubMed

Abernethy, Amy; Abrahams, Edward; Barker, Anna; Buetow, Ken; Burkholder, Randy; Dalton, William S; Foti, Margaret; Frueh, Felix; Gaynor, Richard B; Kean, Marcia; Khan, Zeba; Lessor, Tracy; Lichtenfeld, J Leonard; Mendelsohn, John; van't Veer, Laura

2014-03-01

An ever-expanding understanding of the molecular basis of the more than 200 unique diseases collectively called cancer, combined with efforts to apply these insights to clinical care, is forming the foundation of an era of personalized medicine that promises to improve cancer treatment. At the same time, these extraordinary opportunities are occurring in an environment of intense pressure to contain rising healthcare costs. This environment presents a challenge to oncology research and clinical care, because both are becoming progressively more complex and expensive, and because the current tools to measure the cost and value of advances in care (e.g., comparative effectiveness research, cost-effectiveness analysis, and health technology assessments) are not optimized for an ecosystem moving toward personalized, patient-centered care. Reconciling this tension will be essential to maintaining progress in a cost-constrained environment, especially because emerging innovations in science (e.g., increasing identification of molecular biomarkers) and in clinical process (implementation of a learning healthcare system) hold potential to dramatically improve patient care, and may ultimately help address the burden of rising costs. For example, the rapid pace of innovation taking place within oncology calls for increased capability to integrate clinical research and care to enable continuous learning, so that lessons learned from each patient treated can inform clinical decision making for the next patient. Recognizing the need to define the policies required for sustained innovation in cancer research and care in an era of cost containment, the stakeholder community must engage in an ongoing dialogue and identify areas for collaboration. This article reflects and seeks to amplify the ongoing robust discussion and diverse perspectives brought to this issue by multiple stakeholders within the cancer community, and to consider how to frame the research and regulatory policies necessary to sustain progress against cancer in an environment of constrained resources. ©2014 AACR

Taking Human Capital Seriously: Talented Teachers in Every Classroom, Talented Principals in Every School. Principles and Recommendations for the Strategic Management of Human Capital in Public Education

ERIC Educational Resources Information Center

Consortium for Policy Research in Education, 2009

2009-01-01

The Strategic Management of Human Capital in Education Project was founded in 2008 with one goal: to improve student achievement dramatically in the 100 largest urban school districts. Unless teaching quality and principal leadership improve significantly, lasting education improvement is impossible. In policy terms, without "strategic management"…

Higher Order Language Competence and Adolescent Mental Health

ERIC Educational Resources Information Center

Cohen, Nancy J.; Farnia, Fataneh; Im-Bolter, Nancie

2013-01-01

Background: Clinic and community-based epidemiological studies have shown an association between child psychopathology and language impairment. The demands on language for social and academic adjustment shift dramatically during adolescence and the ability to understand the nonliteral meaning in language represented by higher order language…

Organizational Change. Symposium 11. [Concurrent Symposium Session at AHRD Annual Conference, 2000.

ERIC Educational Resources Information Center

2000

This packet contains three papers from a symposium on organizational change. The first paper, "Kaizen Blitz: Rapid Learning to Facilitate Immediate Organizational Improvements" (Robert B. Gudgel, Fred C. Feitler), describes rapid and dramatic improvement in the organizational performance of a manufacturing firm after use of a series of…

Improving the Education of At-Risk Students. A System of Checks and Balances.

ERIC Educational Resources Information Center

Murphy, John A.

During the last five years, the Prince George's County (Maryland) public school system has brought about dramatic improvements in the academic achievement of at-risk students, offering strong evidence that public education can succeed for all children. This report describes how Prince George's County accomplished this turnaround through a process…

Using Inspections to Improve the Quality of Product Documentation and Code.

ERIC Educational Resources Information Center

Zuchero, John

1995-01-01

Describes how, by adapting software inspections to assess documentation and code, technical writers can collaborate with development personnel, editors, and customers to dramatically improve both the quality of documentation and the very process of inspecting that documentation. Notes that the five steps involved in the inspection process are:…

Improving Student Performance through Computer-Based Assessment: Insights from Recent Research.

ERIC Educational Resources Information Center

Ricketts, C.; Wilks, S. J.

2002-01-01

Compared student performance on computer-based assessment to machine-graded multiple choice tests. Found that performance improved dramatically on the computer-based assessment when students were not required to scroll through the question paper. Concluded that students may be disadvantaged by the introduction of online assessment unless care is…

A Perspective on Primary Prevention in the Earliest Years.

ERIC Educational Resources Information Center

Richmond, Julius B.

The decade of the 70's has seen significant improvements in child health and dramatic insights into the biological, psychological, and social factors influencing children's growth and development. Four of the six major gains in health status listed in the Surgeon General's Report on Health Promotion and Disease Prevention relate to improvements in…

New research and tools lead to improved earthquake alerting protocols

USGS Publications Warehouse

Wald, David J.

2009-01-01

What’s the best way to get alerted about the occurrence and potential impact of an earthquake? The answer to that question has changed dramatically of late, in part due to improvements in earthquake science, and in part by the implementation of new research in the delivery of earthquake information

Challenges in Building Usable Knowledge in Education

ERIC Educational Resources Information Center

Hedges, Larry V.

2018-01-01

The scientific rigor of education research has improved dramatically since the year 2000. Much of the credit for this improvement is deserved by Institute of Education Sciences (IES) policies that helped create a demand for rigorous research; increased human capital capacity to carry out such work; provided funding for the work itself; and…

A Better Blend: A Vision for Boosting Student Outcomes with Digital Learning

ERIC Educational Resources Information Center

Public Impact, 2013

2013-01-01

Blended learning that combines digital instruction with live, accountable teachers holds unique promise to improve student outcomes dramatically. Schools will not realize this promise at large scale with technology improvements alone, though, or with technology and today's typical teaching roles. This brief explains how schools can use blended…

Real Leaders, Real Schools: Stories of Success against Enormous Odds

ERIC Educational Resources Information Center

Leader, Gerald C.

2008-01-01

"Real Leaders, Real Schools" tells the stories of five urban public school principals who led their schools through profound and transformative changes. In each of these cases, their efforts resulted in dramatic improvements in student achievement--improvements that occurred within the current environment of high-stakes tests. The revealing and…

Resource- and Approach-Driven Multidimensional Change: Three-Year Effects of School Improvement Grants

ERIC Educational Resources Information Center

Sun, Min; Penner, Emily K.; Loeb, Susanna

2017-01-01

Hoping to spur dramatic school turnaround, the federal government channeled resources to the country's lowest-performing schools through School Improvement Grants (SIG). However, prior research on SIG effectiveness is limited and focuses primarily on student achievement. This study uses a difference-in-differences strategy to estimate program…

The Benwood Plan: A Lesson in Comprehensive Teacher Reform

ERIC Educational Resources Information Center

Silva, Elena

2008-01-01

Hamilton County, Tennessee, engaged in a multi-year effort to improve teaching in a group of eight central city elementary schools. This reform, known as the Benwood Initiative, was funded with $5 million from the Chattanooga-based Benwood Foundation. Student achievement improved dramatically as a result of this initiative. The Benwood successes…

Self Assembled Dipole Monolayers on CNTs: Effect on Transport and Charge Collection

NASA Astrophysics Data System (ADS)

Cook, Alexander; Lee, Bumsu; Kuznetsov, Alexander; Podzorov, Vitaly; Zakhidov, Anvar

2010-03-01

We propose a method of quickly and dramatically increasing the conductivity of carbon nanotubes via growth of a self assembled monolayer (SAM) of fluoroalkyl trichlorosilane dipoles following the method demonstrated with organic semiconductors in [1,2]. Growth of a SAM on carbon nanotubes results in a strong p-type doping which improves the conductivity by a factor of two or more. Additionally, this doping is nonvolatile and persists in high vacuum and inert atmospheres. Improvements to conductivity are most dramatic in the case of predominantly semi-conducting, single walled carbon nanotubes (SWCNT) due to the remarkable introduction of about 1.2e14 holes/sq. cm, but this method is also an effective means to improve metallic, multi-walled carbon nanotubes (MWCNT). We will demonstrate improvement of transport and charge collection properties of both SWCNTs and MWCNTs by these SAM coatings in FETs and also in organic photovoltaic solar cells and in OLEDs. [1] M. F. Calhoun et al. Nature Materials 7, 84 - 89 (2008). [2] C. Y. Kao et al. Adv. Func. Mater. 19, 1 (2009).

Current state and future direction of computer systems at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Rogers, James L. (Editor); Tucker, Jerry H. (Editor)

1992-01-01

Computer systems have advanced at a rate unmatched by any other area of technology. As performance has dramatically increased there has been an equally dramatic reduction in cost. This constant cost performance improvement has precipitated the pervasiveness of computer systems into virtually all areas of technology. This improvement is due primarily to advances in microelectronics. Most people are now convinced that the new generation of supercomputers will be built using a large number (possibly thousands) of high performance microprocessors. Although the spectacular improvements in computer systems have come about because of these hardware advances, there has also been a steady improvement in software techniques. In an effort to understand how these hardware and software advances will effect research at NASA LaRC, the Computer Systems Technical Committee drafted this white paper to examine the current state and possible future directions of computer systems at the Center. This paper discusses selected important areas of computer systems including real-time systems, embedded systems, high performance computing, distributed computing networks, data acquisition systems, artificial intelligence, and visualization.

Genes and plays: bringing ELSI issues to life.

PubMed

Rothenberg, Karen H; Bush, Lynn W

2012-02-01

Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal, and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To illuminate these enduring concerns, we explore how perceptions and relationships have influenced-and been influenced by-genetics as portrayed through dramatic vignettes. We build on the legacy of using case vignettes as a clinical teaching modality, and believe similar value exists within the research ethics domain. The selection of dialogue discussed encompasses abbreviated excerpts from two existing and one original vignette that we staged at the ELSI 2011 Congress and various academic and health institutions.

Protocol of a Pilot Study of Technology-Enabled Coproduction in Pediatric Chronic Illness Care

PubMed Central

Thakkar, Sunny Narendra; Burns, Lisa; Chini, Barbara; Dykes, Dana MH; McPhail, Gary L; Moore, Erin; Saeed, Shehzad Ahmed; Eslick, Ian; Margolis, Peter A

2017-01-01

Background Pediatric chronic illness care models are traditionally organized around acute episodes of care and may not meet the needs of patients and their families. Interventions that extend the patient-clinician interaction beyond the health care visit, allow for asynchronous and bidirectional feedback loops that span visits and daily life, and facilitate seamless sharing of information are needed to support a care delivery system that is more collaborative, continuous, and data-driven. Orchestra is a mobile health technology platform and intervention designed to transform the management of chronic diseases by optimizing patient-clinician coproduction of care. Objective The aim of this study is to assess the feasibility, acceptability, and preliminary impact of the Orchestra technology and intervention in the context of pediatric chronic illness care. Methods This study will be conducted in the cystic fibrosis and inflammatory bowel disease clinics at Cincinnati Children’s Hospital Medical Center. We will enroll interested patients and their caregivers to work with clinicians to use the Orchestra technology platform and care model over a 6-month period. In parallel, we will use quality improvement methods to improve processes for integrating Orchestra into clinic workflows and patient/family lifestyles. We will use surveys, interviews, technology use data, and measures of clinical outcomes to assess the feasibility, acceptability, and preliminary impact of Orchestra. Outcome measures will include assessments of: (1) enrollment and dropout rates; (2) duration of engagement/sustained use; (3) symptom and patient-reported outcome tracker completion rates; (4) perceived impact on treatment plan, communication with the clinical team, visit preparation, and overall care; (5) changes in disease self-efficacy and engagement in care; and (6) clinical outcomes and health care utilization. Results Participant recruitment began in mid-2015, with results expected in 2017. Conclusions Chronic disease management needs a dramatic transformation to support more collaborative, effective, and patient-centered care. This study is unique in that it is testing not only the impact of technology, but also the necessary processes that facilitate patient and clinician collaboration. This pilot study is designed to examine how technology-enabled coproduction can be implemented in real-life clinical contexts. Once the Orchestra technology and intervention are optimized to ensure feasibility and acceptability, future studies can test the effectiveness of this approach to improve patient outcomes and health care value. PMID:28455274

Ganymede - Comparison of Voyager and Galileo Resolution

NASA Image and Video Library

1997-09-07

These images demonstrate the dramatic improvement in the resolution of pictures that NASA Galileo spacecraft returned compared to previous images of the Jupiter system. http://photojournal.jpl.nasa.gov/catalog/PIA00277

Argonne National Laboratory |

Science.gov Websites

for next-gen lithium batteries. Spotlight New ion source dramatically improves radioactive beams for Argonne's CARIBU facility A new Electron Beam Ion Source Charge Breeder operated with Argonne's CARIBU and

Radiotherapy for Early-Stage Hodgkin's Lymphoma: A 21st Century Perspective and Review of Multiple Randomized Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bar Ad, Voichita; Paltiel, Ora; Glatstein, Eli

2008-12-01

The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin'smore » lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.« less

Low-power polling mode of the next-generation IMES2 implantable wireless EMG sensor.

PubMed

DeMichele, Glenn A; Hu, Zhe; Troyk, Philip R; Chen, Hongnan; Weir, Richard F ff

2014-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee's voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a low-power polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control.

Low-Power Polling Mode of the Next-Generation IMES2 Implantable Wireless EMG Sensor

PubMed Central

DeMichele, Glenn A.; Hu, Zhe; Troyk, Philip R.; Chen, Hongnan; Weir, Richard F. ff.

2015-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee’s voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a lowpower polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control. PMID:25570642

Leucoencephalopathy following abuse of sniffed heroin.

PubMed

Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David

2017-01-01

A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Platforms.

PubMed

Josko, Deborah

2014-01-01

The advent of DNA sequencing technologies and the various applications that can be performed will have a dramatic effect on medicine and healthcare in the near future. There are several DNA sequencing platforms available on the market for research and clinical use. Based on the medical laboratory scientist or researcher's needs and taking into consideration laboratory space and budget, one can chose which platform will be beneficial to their institution and their patient population. Although some of the instrument costs seem high, diagnosing a patient quickly and accurately will save hospitals money with fewer hospital stays and targeted treatment based on an individual's genetic make-up. By determining the type of disease an individual has, based on the mutations present or having the ability to prescribe the appropriate antimicrobials based on the knowledge of the organism's resistance patterns, the clinician will be better able to treat and diagnose a patient which ultimately will improve patient outcomes and prognosis.

Reproductive hazards in the workplace: what the practitioner needs to know about chemical exposures.

PubMed

Paul, M; Himmelstein, J

1988-06-01

A growing body of scientific evidence implicates occupational chemical exposures in the etiology of human adverse reproductive outcomes. Most reproductive toxins that have been investigated in sufficient detail have been shown to exert multiple effects on and through both men and women. In the face of growing public awareness, it is essential that clinicians develop a knowledgeable and effective approach to patient concerns about reproductive hazards in the workplace. Of vital importance is the accurate characterization of exposure at the worksite. Intervention strategies for worrisome situations include amelioration of worksite exposure or, as a last resort, temporary, compensated job modification or transfer. The clinician can obtain assistance in addressing the problem from several resources, including local regulatory agencies and occupational health clinics. Widespread involvement of knowledgeable health professionals can have a dramatic impact on improving this important contemporary public health problem.

G-DRG Version 2009: new developments.

PubMed

Müller, Marcel L; Forschner, Andrea; Wenke, Andreas; Luger, Thomas A; Rompel, Rainer; Roeder, Norbert; Hensen, Peter

2009-04-01

The update of the G-DRG system for the year 2009 has been successfully negotiated. Like in the past years, changes are minimal and not dramatic, but they significantly enhance the quality of the DRG system. Once again, the German DRG system demonstrates its versatility and reliability for clinical reimbursement purposes. In the field of dermatology, several improvements or enhancements can be identified; the average case mix index that declined in the past years should now rise by 0.5 percent for 2009. Oncology cases are affected especially by this increase. Some refinements advanced for several years by the German Dermatologic Society (DDG) have been recognized --complex therapies like vacuum wound therapy, isolation due to multi-resistant infections and multiple primary tumors now have better cost weights. Although there still remain some minor problems like reimbursement of cost-intensive treatments, German dermatology is in summary very well prepared for the year 2009.

Prognostic Physiology: Modeling Patient Severity in Intensive Care Units Using Radial Domain Folding

PubMed Central

Joshi, Rohit; Szolovits, Peter

2012-01-01

Real-time scalable predictive algorithms that can mine big health data as the care is happening can become the new “medical tests” in critical care. This work describes a new unsupervised learning approach, radial domain folding, to scale and summarize the enormous amount of data collected and to visualize the degradations or improvements in multiple organ systems in real time. Our proposed system is based on learning multi-layer lower dimensional abstractions from routinely generated patient data in modern Intensive Care Units (ICUs), and is dramatically different from most of the current work being done in ICU data mining that rely on building supervised predictive models using commonly measured clinical observations. We demonstrate that our system discovers abstract patient states that summarize a patient’s physiology. Further, we show that a logistic regression model trained exclusively on our learned layer outperforms a customized SAPS II score on the mortality prediction task. PMID:23304406

Biologics for the treatment of pyoderma gangrenosum in ulcerative colitis.

PubMed

Arivarasan, K; Bhardwaj, Vaishali; Sud, Sukrit; Sachdeva, Sanjeev; Puri, Amarender Singh

2016-10-01

Pyoderma gangrenosum (PG) is an uncommon extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite limited published literature, biologics have caused a paradigm shift in the management of this difficult-to-treat skin condition. The clinical data and outcomes of three patients with active ulcerative colitis and concurrent PG treated with biologics (infliximab two and adalimumab one) are reviewed in this report. Biologics were added because of the sub-optimal response of the colonic symptoms and skin lesions to parenteral hydrocortisone therapy. All three patients showed a dramatic response to the addition of the biologics. In view of the rapid healing of the skin lesions, superior response rate, and the additional benefit of improvement in the underlying colonic disease following treatment, anti-tumor necrosis factor blockers should be considered as a first line therapy in the management of PG with underlying IBD.

Technology-enhanced caries detection and diagnosis.

PubMed

Strassler, Howard E; Sensi, Luis Guilherme

2008-10-01

The prevalence of dental caries in children and adults in the United States has been declining the past 40 years primarily because of increased use of fluoride, improved oral hygiene and better oral hygiene devices, a greater emphasis on disease prevention and control, and better access to dental care made available by the dental profession. Caries diagnosis and detection for pit-and-fissure lesions has changed dramatically in the past 25 years. Research has confirmed that the carious process is bacterially mediated and is accompanied by changes in salivary flow and pH and the intake of refined carbohydrates. In recent years a number of new technologies have become available as adjuncts to traditional methods of diagnosing carious lesions. While using these new technologies, the clinician still needs to understand the concepts of caries risk, diagnosis, detection, and assessment. Working from the evidence, dental practitioners can decide on a sound clinical diagnosis and treatment plan.

Generalized subcutaneous edema as a rare manifestation of dermatomyositis: clinical lesson from a rare feature.

PubMed

Haroon, Muhammad; Eltahir, Ahmed; Harney, Sinead

2011-04-01

Generalized subcutaneous edema is a very rare manifestation of inflammatory myopathies. A 61-year-old woman presented with classic signs and symptoms of dermatomyositis. She was also noted to have generalized edema that was so florid that an alternative diagnosis was considered. Her disease was resistant to corticosteroids, azathioprine, and mycophenolate mofetil. Intravenous administration of immunoglobulins was started because of marked worsening of her disease-muscle weakness, generalized anasarca, and involvement of her bulbar muscles. This led to dramatic resolution of her subcutaneous edema and significant improvement of her skin and muscle disease. As the initial screen for malignancy was negative, a positron emission tomography-computed tomography scan was requested, which interestingly showed a metabolically active cervical tumor. Anasarca is an unusual manifestation of dermatomyositis. In treatment-refractory cases, it seems reasonable to consider positron emission tomography scan in excluding underlying malignant disease.

Potential mechanisms of cerebellar hypoplasia in prematurity.

PubMed

Tam, Emily W Y

2013-09-01

The cerebellum undergoes dramatic growth and maturation over the neonatal period after preterm birth and is thus particularly sensitive to impaired development due to various clinical factors. Impairments in growth can occur independent of cerebellar parenchymal damage, such as from local hemorrhage, resulting from reduced expression of sonic hedgehog signaling to trigger the appropriate expansion of the granule precursor cells. The primary risk factors for impaired cerebellar development include postnatal glucocorticoid exposure, which has direct effects on the sonic hedgehog pathway, and supratentorial brain injury, including intraventricular hemorrhage and white matter injury, which may result in crossed cerebellar diaschisis and local toxic effects of blood products on the external granular layer. Other cardiorespiratory and nutritional factors may also exist. Impaired cerebellar development is associated with adverse outcomes in motor and cognitive development. New approaches to care to counteract these risk factors may help improve long-term outcome after preterm birth.

Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span

PubMed Central

Losada, Liliana; Amundsen, Cindy L.; Ashton-Miller, James; Chai, Toby; Close, Clare; Damaser, Margot; DiSanto, Michael; Dmochowski, Roger; Fraser, Matthew O.; Kielb, Stephanie J.; Kuchel, George; Mueller, Elizabeth R.; Parker-Autry, Candace; Wolfe, Alan J.

2016-01-01

Abstract Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life. PMID:27285829

A review of interprofessional dissemination and education interventions for recognizing and managing dementia

PubMed Central

Galvin, James E.

2014-01-01

The number of individuals with dementia is expected to increase dramatically over the next 20 years. Given the complicated clinical, sociobehavioral, and caregiving skills that are needed to comprehensively assess and manage individuals with dementia, the gold standard of care requires involvement of an interprofessional team. This systematic review examined 4,023 abstracts, finding 18 papers from 16 studies where an interprofessional dissemination program was performed. Most studies found some improvement in clinician knowledge or confidence, or patient outcomes, though methods and patient and clinician populations were disparate. While a significant evidence base for assessing and managing individuals with dementia has been developed, few studies have examined how to disseminate this research, and even fewer in an interprofessional manner. These findings suggest that greater emphasis needs to be placed on disseminating existing evidence-based care and ensuring that programs are interprofessional in nature so that excellent, patient-centered care is provided. PMID:23879387

Non-traumatic rhabdomyolysis: Background, laboratory features, and acute clinical management.

PubMed

Cervellin, Gianfranco; Comelli, Ivan; Benatti, Mario; Sanchis-Gomar, Fabian; Bassi, Antonella; Lippi, Giuseppe

2017-08-01

Rhabdomyolysis is a relatively rare condition, but its clinical consequences are frequently dramatic in terms of both morbidity and mortality. Although no consensus has been reached so far about the precise definition of this condition, the term rhabdomyolysis describes a rapid breakdown of striated, or skeletal, muscle. It is hence characterized by the rupture and necrosis of muscle fibers, resulting in release of cell degradation products and intracellular elements within the bloodstream and extracellular space. Notably, the percentage of patients with rhabdomyolysis who develop acute kidney injury, the most dramatic consequence, varies from 13% to over 50% according to both the cause and the clinical and organizational setting where they are diagnosed. Despite direct muscle injury (i.e., traumatic rhabdomyolysis) remains the most common cause, additional causes, frequently overlapping, include hypoxic, physical, chemical or biological factors. The conventional triad of symptoms includes muscle pain, weakness and dark urine. The laboratory diagnosis is essentially based on the measurement of biomarkers of muscle injury, being creatine kinase (CK) the biochemical "gold standard" for diagnosis, and myoglobin the "gold standard" for prognostication, especially in patients with non-traumatic rhabdomyolysis. The essential clinical management in the emergency department is based on a targeted intervention to manage the underlying cause, combined with infusion of fluids and eventually sodium bicarbonate. We will present and discuss in this article the pathophysiological and clinical features of non-traumatic rhabdomyolysis, focusing specifically on Emergency Department (ED) management. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Acute effects of alemtuzumab infusion in patients with active relapsing-remitting MS

PubMed Central

Thomas, Katja; Eisele, Judith; Rodriguez-Leal, Francisco Alejandro; Hainke, Undine

2016-01-01

Objective: Alemtuzumab exerts its clinical efficacy by its specific pattern of depletion and repopulation of different immune cells. Beyond long-term immunologic and clinical data, little is known about acute changes in immunologic and routine laboratory parameters and their clinical relevance during the initial alemtuzumab infusion. Methods: Fifteen patients with highly active MS were recruited. In addition to parameters including heart rate, blood pressure, body temperature, and monitoring of adverse events, complete blood cell count, liver enzymes, kidney function, acute-phase proteins, serum cytokine profile, complement activation, peripheral immune cell distribution, and their potential of cytokine release were investigated prior to and after methylprednisolone and after alemtuzumab on each day of alemtuzumab infusion. Results: After the first alemtuzumab infusion, both the total leukocyte and granulocyte counts markedly increased, whereas lymphocyte counts dramatically decreased. In addition to lymphocyte depletion, cell subtypes important for innate immunity also decreased within the first week after alemtuzumab infusion. Although patients reported feeling well, C-reactive protein and procalcitonin peaked at serum levels consistent with septic conditions. Increases in liver enzymes were detected, although kidney function remained stable. Proinflammatory serum cytokine levels clearly rose after the first alemtuzumab infusion. Alemtuzumab led to impaired cytokine release ex vivo in nondepleted cells. Normal clinical parameters and mild adverse events were presented. Conclusions: Dramatic immunologic effects were observed. Standardized infusion procedure and pretreatment management attenuated infusion-related reactions. Alemtuzumab-mediated effects led to artificially altered parameters in standard blood testing. We recommend clinical decision-making based on primarily clinical symptoms within the first alemtuzumab treatment week. PMID:27213173

Clinical Interviewing with Older Adults

ERIC Educational Resources Information Center

Mohlman, Jan; Sirota, Karen Gainer; Papp, Laszlo A.; Staples, Alison M.; King, Arlene; Gorenstein, Ethan E.

2012-01-01

Over the next few decades the older adult population will increase dramatically, and prevalence rates of psychiatric disorders are also expected to increase in the elderly cohort. These demographic projections highlight the need for diagnostic instruments and methods that are specifically tailored to older adults. The current paper discusses the…

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

PubMed

Sakorafas, George H; Smyrniotis, Vasileios

2012-07-10

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the effectiveness of treatment and prognosis of patients with pancreatic cancer. 

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

This factsheet describes a project that developed and demonstrated a new manufacturing-informed design framework that utilizes advanced multi-scale, physics-based process modeling to dramatically improve manufacturing productivity and quality in machining operations while reducing the cost of machined components.

Potential functional applications of extracellular vesicles: a report by the NIH Common Fund Extracellular RNA Communication Consortium

PubMed Central

Quesenberry, Peter J.; Aliotta, Jason; Camussi, Giovanni; Abdel-Mageed, Asim B.; Wen, Sicheng; Goldberg, Laura; Zhang, Huang-Ge; Tetta, Ciro; Franklin, Jeffrey; Coffey, Robert J.; Danielson, Kirsty; Subramanya, Vinita; Ghiran, Ionita; Das, Saumya; Chen, Clark C.; Pusic, Kae M.; Pusic, Aya D.; Chatterjee, Devasis; Kraig, Richard P.; Balaj, Leonora; Dooner, Mark

2015-01-01

The NIH Extracellular RNA Communication Program's initiative on clinical utility of extracellular RNAs and therapeutic agents and developing scalable technologies is reviewed here. Background information and details of the projects are presented. The work has focused on modulation of target cell fate by extracellular vesicles (EVs) and RNA. Work on plant-derived vesicles is of intense interest, and non-mammalian sources of vesicles may represent a very promising source for different therapeutic approaches. Retro-viral-like particles are intriguing. Clearly, EVs share pathways with the assembly machinery of several other viruses, including human endogenous retrovirals (HERVs), and this convergence may explain the observation of viral-like particles containing viral proteins and nucleic acid in EVs. Dramatic effect on regeneration of damaged bone marrow, renal, pulmonary and cardiovascular tissue is demonstrated and discussed. These studies show restoration of injured cell function and the importance of heterogeneity of different vesicle populations. The potential for neural regeneration is explored, and the capacity to promote and reverse neoplasia by EV exposure is described. The tremendous clinical potential of EVs underlies many of these projects, and the importance of regulatory issues and the necessity of general manufacturing production (GMP) studies for eventual clinical trials are emphasized. Clinical trials are already being pursued and should expand dramatically in the near future. PMID:26320942

Rapid-cycle testing cuts bed turnaround by 85%.

PubMed

2004-11-01

You can use rapid-cycle testing to try out new approaches to overcrowding much more frequently than with more traditional process improvement strategies. Improving bed turnaround notification can yield dramatic improvements. Telling staff they have to try a new process only for three days makes it easier to gain buy-in. Look for old policies that are no longer needed, yet continue to keep your staff bogged down.

Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollock, Sean, E-mail: sean.pollock@sydney.edu.au; Keall, Paul; Keall, Robyn

Purpose: The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions withinmore » the fields of radiation oncology and radiology. Methods: From August 1–14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. Results: The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. Conclusions: There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the clinical impact of breathing guidance, along with the health technology assessment to determine the advantages and disadvantages of breathing guidance.« less

Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies.

PubMed

Pollock, Sean; Keall, Robyn; Keall, Paul

2015-09-01

The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. From August 1-14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the clinical impact of breathing guidance, along with the health technology assessment to determine the advantages and disadvantages of breathing guidance.

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment

PubMed Central

Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary K.; Gonenc, Atilla; Smith, Rosemary T.; Lambros, Ashley M.; Cabrera, Korine B.; Lukas, Scott E.

2018-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use. PMID:29387010

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

PubMed

Gruber, Staci A; Sagar, Kelly A; Dahlgren, Mary K; Gonenc, Atilla; Smith, Rosemary T; Lambros, Ashley M; Cabrera, Korine B; Lukas, Scott E

2017-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

A Century of Children's Health and Well-Being. Child Trends Research Brief.

ERIC Educational Resources Information Center

Brown, Brett V.; Kinkukawa, Akemi; Michelsen, Erik; Moore, Amber; Moore, Kristin Anderson; Sugland, Barbara W.

Although the last 100 years have seen dramatic improvements in the health of U.S. children, there remain racial and ethnic disparities. This research brief presents data illustrating improvements in children's health and the need for further progress. The brief also examines new morbidities among American youth, such as obesity, early sexual…

Federal School Improvement Grants (SIGs): How Capacity and Local Conditions Matter

ERIC Educational Resources Information Center

Yatsko, Sarah; Lake, Robin; Bowen, Melissa; Cooley Nelson, Elizabeth

2015-01-01

In 2009, the federal government committed over $3 billion nationwide to help states and districts turn around their worst-performing schools. The U.S. Department of Education intended for the School Improvement Grants (SIGs) to spur dramatic change.This report looks at the results of a field study of the first-year implementation of those grants…

Tinkering toward Transformation: A Look at Federal School Improvement Grant Implementation

ERIC Educational Resources Information Center

Yatsko, Sarah; Lake, Robin; Nelson, Elizabeth Cooley; Bowen, Melissa

2012-01-01

In 2009, the federal government committed over $3 billion nationwide to help states and districts turn around their worst-performing schools. The U.S. Department of Education intended for the School Improvement Grants (SIGs) to spur dramatic change. This report looks at the results of a field study of the first-year implementation of those grants…

Changing the School Climate Is the First Step to Reform in Many Schools with Federal Improvement Grants

ERIC Educational Resources Information Center

McMurrer, Jennifer

2012-01-01

School Improvement Grants (SIGs) financed through the economic stimulus package are intended to spur dramatic change in persistently low-performing schools. Many state and local officials charged with implementing SIGs view the creation of a safe, orderly, collegial, and productive school climate as an essential step in raising student…

Power and Leader Effectiveness in Organizations: A Literature Review

DTIC Science & Technology

2008-09-01

cinema and television as dramatic, memorable verbal reprimands for poor performance or an unaccomplished mission. However, coercive power does not...character played by Michael Keaton improved American automotive plant efficiency by improving working relations between the Japanese management and...attraction between the Japanese management and the American laborers. The relational benefits translated into happier employees that were more

Pain, Nicotine, and Smoking: Research Findings and Mechanistic Considerations

ERIC Educational Resources Information Center

Ditre, Joseph W.; Brandon, Thomas H.; Zale, Emily L.; Meagher, Mary M.

2011-01-01

Tobacco addiction and chronic pain represent 2 highly prevalent and comorbid conditions that engender substantial burdens upon individuals and systems. Interrelations between pain and smoking have been of clinical and empirical interest for decades, and research in this area has increased dramatically over the past 5 years. We conceptualize the…

Name Changes in Medically Important Fungi and Their Implications for Clinical Practice

PubMed Central

de Hoog, G. Sybren; Chaturvedi, Vishnu; Denning, David W.; Dyer, Paul S.; Frisvad, Jens Christian; Geiser, David; Gräser, Yvonne; Guarro, Josep; Haase, Gerhard; Kwon-Chung, Kyung-Joo; Meyer, Wieland; Pitt, John I.; Samson, Robert A.; Tintelnot, Kathrin; Vitale, Roxana G.; Walsh, Thomas J.

2014-01-01

Recent changes in the Fungal Code of Nomenclature and developments in molecular phylogeny are about to lead to dramatic changes in the naming of medically important molds and yeasts. In this article, we present a widely supported and simple proposal to prevent unnecessary nomenclatural instability. PMID:25297326

Treating Cancer with Amplitude-Modulated Electromagnetic Fields: A Potential Paradigm Shift, Again?

EPA Science Inventory

The Zimmerman et al. (2011) study published here, coupled with the group's two preceding papers (Barbault et al. (2009), Costa et al. (2011)), identify a potential modality for treating tumors at a dramatic reduction in trauma and cost. This set of clinical and explanatory labora...

Anger Control Bibliotherapy with a Convicted Murderer under Life Sentence: A Clinical Report.

ERIC Educational Resources Information Center

Daniel, Chris

1992-01-01

Used personalized bibliotherapy intervention approach to prevent build up of aggression in inmate with low tolerance to perceived provocation. Follow-up data over six-month period revealed dramatic decrease in discipline reports following therapy. Interview and questionnaire feedback from client indicated reduced incidence of feelings of…

Cryptosporidium surveillance and risk factors in the United States.

PubMed

Yoder, Jonathan S; Beach, Michael J

2010-01-01

Surveillance for Cryptosporidium in the United States indicates that the reported incidence of infection has increased dramatically since 2004. The reasons for this increase are unclear but might be caused by an actual increase in incidence, improved surveillance, improved awareness about cryptosporidiosis, and/or increases in testing practices resulting from the licensing of the first-ever treatment for cryptosporidiosis. While regional differences remain, the incidence of cryptosporidiosis appears to be increasing across the United States. Onset of illness is most common during the summer, particularly among younger children. Cryptosporidiosis case reporting also influences outbreak detection and reporting; the recent rise in cases coincides with an increase in the number of reported cryptosporidiosis outbreaks, particularly in treated recreational water venues. Risk factors include ingesting contaminated recreational or drinking water, exposure to infected animals, having close contacts with cryptosporidiosis, travel to disease-endemic areas, and ingestion of contaminated food. Advances in molecular characterization of clinical specimens have improved our understanding of the changing epidemiology and risk factors. Prevention and control of cryptosporidiosis requires continued efforts to interrupt the transmission of Cryptosporidium through water, food, and contact with infected persons or animals. Of particular importance is continued improvement and monitoring of drinking water treatment and advances in the design, operation, and management of recreational water venues coupled with behavioral changes among the swimming public. Published by Elsevier Inc.

Pharmacophore-Based Similarity Scoring for DOCK

PubMed Central

2015-01-01

Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein–ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK. PMID:25229837

Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp.

PubMed

Leib, Michael S; Duncan, Robert B; Ward, Daniel L

2007-01-01

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists.

PubMed

Deming, Paulina; Martin, Michelle T; Chan, Juliana; Dilworth, Thomas J; El-Lababidi, Rania; Love, Bryan L; Mohammad, Rima A; Nguyen, Amy; Spooner, Linda M; Wortman, Suzanne B

2016-02-01

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one-time HCV screening for all patients born between 1945 and 1965, in addition to risk factor-based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct-acting antivirals. The approval of ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment-naïve and treatment-experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance-associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes. © 2016 Pharmacotherapy Publications, Inc.

Quantification of lung microstructure with hyperpolarized 3He diffusion MRI

PubMed Central

Sukstanskii, Alexander L.; Woods, Jason C.; Gierada, David S.; Quirk, James D.; Hogg, James C.; Cooper, Joel D.; Conradi, Mark S.

2009-01-01

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized 3He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii—parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials. PMID:19661452

Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014.

PubMed

Huo, Hai-zhong; Zhou, Zhi-yuan; Wang, Bing; Qin, Jian; Liu, Wen-yong; Gu, Yan

2014-01-10

Colorectal cancer is a major contributor of cancer-related mortality. The mammalian target or rapamycin (mTOR) signaling is frequently hyper-activated in colorectal cancers, promoting cancer progression and chemo-resistance. In the current study, we investigated the anti-colorectal cancer effect of a novel mTOR complex 1 (mTORC1) and mTORC2 dual inhibitor: AZD-2014. In cultured colorectal cancer cell lines, AZD-2014 significantly inhibited cancer cell growth without inducing significant cell apoptosis. AZD-2014 blocked activation of both mTORC1 (S6K and S6 phosphorylation) and mTORC2 (Akt Ser 473 phosphorylation), and activated autophagy in colorectal cancer cells. Meanwhile, autophagy inhibition by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the apoptosis inhibitor had no rescue effect. In vivo, AZD-2014 oral administration significantly inhibited the growth of HT-29 cell xenograft in SCID mice, and the mice survival was dramatically improved. At the same time, in xenografted tumors administrated with AZD-2014, the activation of mTORC1 and mTORC2 were largely inhibited, and autophagic markers were significantly increased. Thus, AZD-2014 inhibits colorectal cancer cell growth both in vivo and in vitro. Our results suggest that AZD-2014 may be further investigated for colorectal cancer therapy in clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal treatment of Down syndrome: a reality?

PubMed

Guedj, Fayçal; Bianchi, Diana W; Delabar, Jean-Maurice

2014-04-01

Down syndrome affects more than 5 million people globally. During the last 10 years, there has been a dramatic increase in the research efforts focused on therapeutic interventions to improve learning and memory in Down syndrome. This review summarizes the different functional abnormalities targeted by researchers in mouse models of Down syndrome. Three main strategies have been used: neural stem cell implantation; environmental enrichment and physical exercise; and pharmacotherapy. Pharmacological targets include the choline pathway, GABA and NMDA receptors, DYRK1A protein, oxidative stress and pathways involved in development and neurogenesis. Many strategies have improved learning and memory as well as electrophysiological and molecular alterations in affected animals. To date, eight molecules have been tested in human adult clinical trials. No studies have yet been performed on infants. However, compelling studies reveal that permanent brain alterations originate during fetal life in Down syndrome. Early prenatal diagnosis offers a 28 weeks window to positively impact brain development and improve postnatal cognitive outcome in affected individuals. Only a few approaches (Epigallocatechine gallate, NAP/SAL, fluoxetine, and apigenin) have been used to treat mice in utero; these showed therapeutic effects that persisted to adulthood. In this article, we discuss the challenges, recent progress, and lessons learned that pave the way for new therapeutic approaches in Down syndrome.

Therapeutic drug monitoring in patients with inflammatory bowel disease

PubMed Central

Yarur, Andres J; Abreu, Maria T; Deshpande, Amar R; Kerman, David H; Sussman, Daniel A

2014-01-01

Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients’ pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care. PMID:24707130

RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Rau, Julietta V.; Graziani, Valerio; Fosca, Marco; Taffon, Chiara; Rocchia, Massimiliano; Crucitti, Pierfilippo; Pozzilli, Paolo; Onetti Muda, Andrea; Caricato, Marco; Crescenzi, Anna

2016-10-01

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.

Postpneumonectomy syndrome in children: advantages and long-term follow-up of expandable prosthesis.

PubMed

Podevin, G; Larroquet, M; Camby, C; Audry, G; Plattner, V; Heloury, Y

2001-09-01

Pneumonectomy in children can be complicated by a severe mediastinal shift, which leads to bronchial stretching resulting in severe respiratory failure. This postpneumonectomy syndrome can be corrected by inserting a prosthesis in the empty side of the chest. Forty-two children, from 6 months to 15 years old, underwent a pneumonectomy. Seven of these patients were treated surgically for severe manifestations of postpneumonectomy syndrome. First insertion of an expandable prosthesis was followed up in 5 cases by its replacement with a breast prosthesis in adolescence. The expandable prosthesis was injected periodically with saline solution to maintain the mediastinum in a midline position as the children grew. The mean delay between pneumonectomy and first prosthesis implantation was 5 years (range, 11 months to 8 years). Pulmonary function tests showed a substantial improvement in the obstructive syndrome in all patients except one, in whom the functional improvement was moderate. The mean follow-up after the expandable prosthesis implantation was 6 years (range, 6 months to 10 years) and all patients are doing well. The insertion of an intrathoracic prosthesis can dramatically improve the clinical symptoms and reduce the functional obstructive syndrome. The expandable prosthesis allowed for progressive, well-tolerated recentering of the mediastinum and adjustment for growth. Copyright 2001 by W.B. Saunders Company.

Hyperlipidemia secondary to acitretin therapy for lamellar ichthyosis associated with a NIPAL4 mutation improves on a plant-based diet and relapses on a standard Western diet.

PubMed

Lin, Jonathan C; Massera, Daniele; Ghalib, Mohammad; Marion, Robert; Graf, Lauren; Cohen, Steven R; Ostfeld, Robert J

2018-04-01

Oral retinoids are commonly prescribed for many dermatological conditions and may induce hyperlipidemia. We document the case of a 35-year-old man taking acitretin for congenital lamellar ichthyosis associated with a homozygous deleterious mutation in NIPAL4 who developed retinoid-induced hyperlipidemia that responded dramatically to a whole-food plant-based (WFPB) diet. On presentation, his diet consisted of chicken, fish, low fat meats and dairy, grains, and some fruits and vegetables. He then adopted a WFPB diet without making changes to his medications. His serum lipid levels dropped and his exercise capacity improved. Five months later, after discontinuing the plant-based diet and returning to his baseline diet, his hyperlipidemia returned and persisted despite adjustments to his medications. After a year and a half, the patient again adopted a plant-based diet and his lipid levels fell sharply again. A WFPB diet helped improve and control serum lipid levels in a patient with retinoid-induced hyperlipidemia. Future interventions should focus on ways to help patients successfully adopt and maintain a WFPB diet, as increased adherence to a healthy lifestyle is associated with greater health benefits. Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

PubMed Central

Smith, J. Joshua; Garcia-Aguilar, Julio

2015-01-01

Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

Dramatic weight loss associated with commencing clozapine.

PubMed

Lally, John; McDonald, Colm

2011-11-08

The authors report the case of a 44-year-old man with a long history of chronic enduring schizophrenia who experienced dramatic weight loss after commencing treatment with clozapine, an antipsychotic medication characteristically associated with the greatest degree of weight gain among medical treatments for schizophrenia. He was obese with a body mass index (BMI) of 41.5 kg/m(2), but after commencing clozapine therapy he experienced an improvement in psychotic symptoms and 40% loss of his body weight attained through an altered diet and exercise regime, which resulted in him attaining a normal BMI of 24.8 kg/m(2).

AIDS Myths and Misunderstandings

MedlinePlus

... get infected. Reality: today’s medications have cut the death rate from AIDS by about 80%. They are also ... In the 1980s, there was a very high death rate from AIDS. However, medications have improved dramatically and ...

Prep-ME Software Implementation and Enhancement

DOT National Transportation Integrated Search

2017-09-01

Highway agencies across the United States are moving from empirical design procedures towards the mechanistic-empirical (ME) based pavement design. Even though the Pavement ME Design presents a new paradigm shift with several dramatic improvements, i...

History of solid organ transplantation and organ donation.

PubMed

Linden, Peter K

2009-01-01

Solid organ transplantation is one of the most remarkable and dramatic therapeutic advances in medicine during the past 60 years. This field has progressed initially from what can accurately be termed a "clinical experiment" to routine and reliable practice, which has proven to be clinically effective, life-saving and cost-effective. This remarkable evolution stems from a serial confluence of: cultural acceptance; legal and political evolution to facilitate organ donation, procurement and allocation; technical and cognitive advances in organ preservation, surgery, immunology, immunosuppression; and management of infectious diseases. Some of the major milestones of this multidisciplinary clinical science are reviewed in this article.

Methicillin-resistant Staphylococcus aureus and skin infections among personnel at a pediatric clinic.

PubMed

Carpenter, L Rand; Kainer, Marion; Woron, Amy; Schaffner, William; Jones, Timothy F

2008-11-01

Ambulatory care visits for methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing dramatically. We investigated a pediatric clinic worker's death caused by MRSA. Among 45 clinic personnel, 16 reported recent skin infections, and 4% were colonized with MRSA. Among 262 patients, 3.4% were colonized with MRSA. Standard precautions were inconsistently applied when treating skin infections. Eight (11%) of 71 environmental swipes contained S aureus. Health care workers in outpatient settings are increasingly exposed to substantial numbers of persons with MRSA, and infection control practices in the ambulatory care setting deserve reemphasis.

Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy.

PubMed

Caillot, Noémie; Bouley, Julien; Jain, Karine; Mariano, Sandrine; Luce, Sonia; Horiot, Stéphane; Airouche, Sabi; Beuraud, Chloé; Beauvallet, Christian; Devillier, Philippe; Chollet-Martin, Sylvie; Kellenberger, Christine; Mascarell, Laurent; Chabre, Henri; Batard, Thierry; Nony, Emmanuel; Lombardi, Vincent; Baron-Bodo, Véronique; Moingeon, Philippe

2017-09-01

Eligibility to immunotherapy is based on the determination of IgE reactivity to a specific allergen by means of skin prick or in vitro testing. Biomarkers predicting the likelihood of clinical improvement during immunotherapy would significantly improve patient selection. Proteins were differentially assessed by using 2-dimensional differential gel electrophoresis and label-free mass spectrometry in pretreatment sera obtained from clinical responders and nonresponders within a cohort of 82 patients with grass pollen allergy receiving sublingual immunotherapy or placebo. Functional studies of Fetuin-A (FetA) were conducted by using gene silencing in a mouse asthma model, human dendritic cell in vitro stimulation assays, and surface plasmon resonance. Analysis by using quantitative proteomics of pretreatment sera from patients with grass pollen allergy reveals that high levels of O-glycosylated sialylated FetA isoforms are found in patients exhibiting a strong decrease in rhinoconjunctivitis symptoms after sublingual immunotherapy. Although FetA is involved in numerous inflammatory conditions, its potential role in allergy is unknown. In vivo silencing of the FETUA gene in BALB/c mice results in a dramatic upregulation of airway hyperresponsiveness, lung resistance, and T H 2 responses after allergic sensitization to ovalbumin. Both sialylated and nonsialytated FetA bind to LPS, but only the former synergizes with LPS and grass pollen or mite allergens to enhance the Toll-like receptor 4-mediated proallergic properties of human dendritic cells. As a reflection of the patient's inflammatory status, pretreatment levels of sialylated FetA in the blood are indicative of the likelihood of clinical responses during grass pollen immunotherapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Developing a knowledge base to support the annotation of ultrasound images of ectopic pregnancy.

PubMed

Dhombres, Ferdinand; Maurice, Paul; Friszer, Stéphanie; Guilbaud, Lucie; Lelong, Nathalie; Khoshnood, Babak; Charlet, Jean; Perrot, Nicolas; Jauniaux, Eric; Jurkovic, Davor; Jouannic, Jean-Marie

2017-01-31

Ectopic pregnancy is a frequent early complication of pregnancy associated with significant rates of morbidly and mortality. The positive diagnosis of this condition is established through transvaginal ultrasound scanning. The timing of diagnosis depends on the operator expertise in identifying the signs of ectopic pregnancy, which varies dramatically among medical staff with heterogeneous training. Developing decision support systems in this context is expected to improve the identification of these signs and subsequently improve the quality of care. In this article, we present a new knowledge base for ectopic pregnancy, and we demonstrate its use on the annotation of clinical images. The knowledge base is supported by an application ontology, which provides the taxonomy, the vocabulary and definitions for 24 types and 81 signs of ectopic pregnancy, 484 anatomical structures and 32 technical elements for image acquisition. The knowledge base provides a sign-centric model of the domain, with the relations of signs to ectopic pregnancy types, anatomical structures and the technical elements. The evaluation of the ontology and knowledge base demonstrated a positive feedback from a panel of 17 medical users. Leveraging these semantic resources, we developed an application for the annotation of ultrasound images. Using this application, 6 operators achieved a precision of 0.83 for the identification of signs in 208 ultrasound images corresponding to 35 clinical cases of ectopic pregnancy. We developed a new ectopic pregnancy knowledge base for the annotation of ultrasound images. The use of this knowledge base for the annotation of ultrasound images of ectopic pregnancy showed promising results from the perspective of clinical decision support system development. Other gynecological disorders and fetal anomalies may benefit from our approach.

Potentiator Ivacaftor Abrogates Pharmacological Correction of ΔF508 CFTR in Cystic Fibrosis

PubMed Central

Cholon, Deborah M.; Quinney, Nancy L.; Fulcher, M. Leslie; Esther, Charles R.; Das, Jhuma; Dokholyan, Nikolay V.; Randell, Scott H.; Boucher, Richard C.; Gentzsch, Martina

2014-01-01

Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR). Newly developed “correctors” such as lumacaftor (VX-809) that improve CFTR maturation and trafficking and “potentiators” such as ivacaftor (VX-770) that enhance channel activity may provide important advances in CF therapy. Although VX-770 has demonstrated substantial clinical efficacy in the small subset of patients with a mutation (G551D) that affects only channel activity, a single compound is not sufficient to treat patients with the more common CFTR mutation, ΔF508. Thus, patients with ΔF508 will likely require treatment with both correctors and potentiators to achieve clinical benefit. However, whereas the effectiveness of acute treatment with this drug combination has been demonstrated in vitro, the impact of chronic therapy has not been established. In studies of human primary airway epithelial cells, we found that both acute and chronic treatment with VX-770 improved CFTR function in cells with the G551D mutation, consistent with clinical studies. In contrast, chronic VX-770 administration caused a dose-dependent reversal of VX-809-mediated CFTR correction in ΔF508 homozygous cultures. This result reflected the destabilization of corrected ΔF508 CFTR by VX-770, dramatically increasing its turnover rate. Chronic VX-770 treatment also reduced mature wild-type CFTR levels and function. These findings demonstrate that chronic treatment with CFTR potentiators and correctors may have unexpected effects that cannot be predicted from short-term studies. Combining of these drugs to maximize rescue of ΔF508 CFTR may require changes in dosing and/or development of new potentiator compounds that do not interfere with CFTR stability. PMID:25101886

Methodological issues in the design of clinical trials for the treatment of multidrug-resistant tuberculosis: challenges and opportunities.

PubMed

Lienhardt, C; Davies, G

2010-05-01

The burden of multidrug-resistant tuberculosis (MDR-TB) is increasing dramatically in the world today, severely hampering global TB control. Treatment of MDR-TB is complex, prolonged, expensive and requires appropriate clinical and laboratory infrastructure. The majority of MDR-TB patients still do not have access to adequate diagnostic services or quality assured second-line drugs, leading to high levels of morbidity and mortality. More effective and efficient MDR-TB treatment with reduced toxicity that could be safely delivered to patients co-infected with human immunodeficiency virus (HIV) is an urgent research priority that could be cost-saving for health systems overall. In this context, understanding how best to design and execute randomised controlled trials to improve MDR-TB treatment has taken on new urgency, to identify the optimal combination(s) of existing and new drugs to assemble in efficient and safe regimen(s), preferably of short duration, that can be easily delivered to patients and safely combined with antiretroviral treatment. In the present report, we address the methodological issues in the design and execution of Phase II and Phase III trials arising from this goal. We suggest that a rational selection of appropriate designs and outcome measures, associated with the application of new diagnostic technology, could overcome many of the methodological and logistical problems. These advances could be key to historic improvements in the treatment of patients suffering from MDR-TB, and perhaps ultimately drug-susceptible TB. As with HIV, clinical trials in patients with drug-resistant disease may provide a quicker and less expensive path to licensure than trials for treatment of drug-susceptible disease.

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

PubMed Central

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-01-01

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome. PMID:29844868

Maximizing retention with high risk participants in a clinical trial.

PubMed

Kim, Romina; Hickman, Norval; Gali, Kathleen; Orozco, Nicholas; Prochaska, Judith J

2014-01-01

To describe effective retention strategies in a clinical trial with a high risk, low-income, and vulnerable patient population with serious mental illness. Follow-up assessments were conducted for a randomized clinical tobacco treatment trial at 3, 6, and 12 months postbaseline. Initial follow-up rates of <40% at 3 months led to implementation of proactive retention strategies including obtaining extensive contact information; building relationships with case managers and social workers; contacting jails and prisons; text messaging, e-mailing, and messaging via social networking sites; identifying appointments via electronic medical record; and field outreach to treatment facilities, residences, and parks. Large urban public hospital. Participants were current smokers recruited from 100% smoke-free locked psychiatry units. Assessments covered demographics, substance use, and mental health functioning. Retention rates were plotted over time in relation to key retention strategies. Chi-square and t-tests were used to examine participant predictors of retention at each follow-up. At the 12-month follow-up, the retention strategies that most frequently led to assessment completion were identified. The sample (N = 100) was 65% male; age x = 39.5 years (SD = 11.3); 44% non-Hispanic white; 46% on Medicaid and 34% uninsured; 79% unemployed; and 48% unstably housed. Proactive retention strategies dramatically increased follow-up rates, concluding at 3 months = 82.65%, 6 months = 89.69%, and 12 months = 92.78%. Married and divorced/separated/widowed participants, those with higher income, and participants with alcohol or illicit drug problems had increased retention from 3- to 12-month follow-up. Follow-up rates improved as proactive methods to contact participants were implemented. Dedicated research staff, multiple methods, community networking, and outreach within drug treatment settings improved retention.

Clinical Holistic Medicine (Mindful, Short-Term Psychodynamic Psychotherapy Complemented with Bodywork) in the Treatment of Experienced Physical Illness and Chronic Pain

PubMed Central

Ventegodt, Søren; Thegler, Suzette; Andreasen, Tove; Struve, Flemming; Enevoldsen, Lars; Bassaine, Laila; Torp, Margrethe; Merrick, Joav

2007-01-01

We investigated the treatment effect of psychodynamic short-term therapy complemented with bodywork on patients who presented with physical illness at the Research Clinic for Holistic Medicine in Copenhagen. Psychodynamic short-term therapy was complemented with bodywork (Marion Rosen) to help patients confront old emotional pain from childhood trauma(s). Patients were measured with a five-item quality of life and health questionnaire (QOL5), a one-item questionnaire of self-assessed quality of life (QOL1), and four questions on self-rated ability to love and to function sexually, socially, and at work (ability to sustain a full-time job). Most of the patients had chronic pain that could not be alleviated with drugs. Results showed that 31 patients with the experience of being severely physically ill (mostly from chronic pain), in spite of having consulted their own general practitioner, entered the study. The holistic approach and body therapy accelerated the therapy dramatically and no significant side effects were detected. After the intervention, 38.7% did not feel ill (1.73 < NNT < 4.58) (p = 0.05). Psychodynamic short-term therapy complemented with bodywork can help patients. When the patients responded to the therapy, the self-assessed mental health, relationship with partner, ability to work, self-assessed quality of life, relationships in general, measured QOL (with the validated questionnaire QOL5), and life's total state (mean of health, QOL and ability) were significantly improved, statistically and clinically. Most importantly, all aspects of life were improved simultaneously, due to induction of Antonovsky-salutogenesis. The patients received in average 20 sessions over 14 months at a cost of 1600 EURO. For the treatment responders, the treatment seemingly provided lasting benefits. PMID:17334622

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.

PubMed

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-05-08

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement ( p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC ( p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.

Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele

PubMed Central

Brown, Erin G.; Lankford, Lee; Keller, Benjamin A.; Pivetti, Christopher D.; Sitkin, Nicole A.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Farmer, Diana L.

2015-01-01

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients. Significance This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC. PMID:25911465

Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

PubMed

Hasford, J; Lamprecht, T

1998-01-01

Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

Bricks-and-mortar and patient safety culture.

PubMed

Brandis, Susan; Schleimer, Stephanie; Rice, John

2017-06-19

Purpose Building a new hospital requires a major investment in capital infrastructure. The purpose of this paper is to investigate the impact of bricks-and-mortar on patient safety culture before and two years after the move of a large tertiary hospital to a greenfield site. The difference in patient safety perceptions between clinical and non-clinical staff is also explored. Design/methodology/approach This research uses data collected from the same workforce across two time periods (2013 and 2015) in a large Australian healthcare service. Validated surveys of patient safety culture ( n=306 and 246) were analysed using descriptive and inferential statistics. Findings Using two-way analysis of variance, the authors found that perceived patient safety culture remains unchanged for staff despite a major relocation and upgrade of services and different perceptions of patient safety culture between staff groups remains the same throughout change. Practical implications A dramatic change in physical context, such as moving an entire hospital, made no measurable impact on perceived patient safety culture by major groups of staff. Improving patient safety culture requires more than investment in buildings and infrastructure. Understanding differences in professional perspectives of patient safety culture may inform organisational management approaches, and enhance the targeting of specific strategies. Originality/value The authors believe this to be the first empirically based paper that investigates the impact of a large investment into hospital capital and a subsequent relocation of services on clinical and non-clinical staff perceptions of patient safety culture.

Photoplethysmography revisited: from contact to noncontact, from point to imaging ♠

PubMed Central

Thakor, Nitish

2016-01-01

Photoplethysmography (PPG) is a non-invasive optical technique for detecting microvascular blood volume changes in tissues. Its ease of use, low cost and convenience make it an attractive area of research in the biomedical and clinical communities. Nevertheless, its single spot monitoring and the need to apply a PPG sensor directly to the skin limit its practicality in situations such as perfusion mapping and healing assessments or when free movement is required. The introduction of fast digital cameras into clinical imaging monitoring and diagnosis systems, the desire to reduce the physical restrictions, and the possible new insights that might come from perfusion imaging and mapping inspired the evolution of conventional PPG technology to imaging PPG (IPPG). IPPG is a noncontact method that can detect heart-generated pulse waves by means of peripheral blood perfusion measurements. Since its inception, IPPG has attracted significant public interest and provided opportunities to improve personal healthcare. This study presents an overview of the wide range of IPPG systems currently being introduced along with examples of their application in various physiological assessments. We believe that the widespread acceptance of IPPG is happening, and it will dramatically accelerate the promotion of this healthcare model in the near future. PMID:26390439

Exocrine and endocrine pancreatic function in 21 patients suffering from autoimmune pancreatitis before and after steroid treatment.

PubMed

Frulloni, Luca; Scattolini, Chiara; Katsotourchi, Anna Maria; Amodio, Antonio; Gabbrielli, Armando; Zamboni, Giuseppe; Benini, Luigi; Vantini, Italo

2010-01-01

Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 +/- 16.5 years) diagnosed as having AIP between 2006 and 2008. At clinical onset, fecal elastase 1 was 107 +/- 126 microg/g stool. Thirteen patients (62%) showed severe pancreatic insufficiency (<100 microg/g stool), 4 (19%) had mild insufficiency (100-200 microg/g stool), while 4 (19%) had normal pancreatic function (>200 microg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (<19 microg/g stool). Following steroids, fecal elastase 1 increased in all patients (237 +/- 193 microg/g stool) and observed levels were significantly higher than those seen before steroids (p = 0.001). Patients suffering from AIP display exocrine and/or endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy. Copyright 2010 S. Karger AG, Basel.

[Development of a microbiology data warehouse (Akita-ReNICS) for networking hospitals in a medical region].

PubMed

Ueki, Shigeharu; Kayaba, Hiroyuki; Tomita, Noriko; Kobayashi, Noriko; Takahashi, Tomoe; Obara, Toshikage; Takeda, Masahide; Moritoki, Yuki; Itoga, Masamichi; Ito, Wataru; Ohsaga, Atsushi; Kondoh, Katsuyuki; Chihara, Junichi

2011-04-01

The active involvement of hospital laboratory in surveillance is crucial to the success of nosocomial infection control. The recent dramatic increase of antimicrobial-resistant organisms and their spread into the community suggest that the infection control strategy of independent medical institutions is insufficient. To share the clinical data and surveillance in our local medical region, we developed a microbiology data warehouse for networking hospital laboratories in Akita prefecture. This system, named Akita-ReNICS, is an easy-to-use information management system designed to compare, track, and report the occurrence of antimicrobial-resistant organisms. Participating laboratories routinely transfer their coded and formatted microbiology data to ReNICS server located at Akita University Hospital from their health care system's clinical computer applications over the internet. We established the system to automate the statistical processes, so that the participants can access the server to monitor graphical data in the manner they prefer, using their own computer's browser. Furthermore, our system also provides the documents server, microbiology and antimicrobiotic database, and space for long-term storage of microbiological samples. Akita-ReNICS could be a next generation network for quality improvement of infection control.

Exercise Training for Persons with Alzheimer's Disease and Caregivers: A Review of Dyadic Exercise Interventions.

PubMed

Lamotte, Guillaume; Shah, Raj C; Lazarov, Orly; Corcos, Daniel M

2017-01-01

Alzheimer's disease (AD) is the most common form of dementia and the prevalence will increase dramatically in the next decades. Although exercise has shown benefits for people with dementia due to AD as well as their caregivers, the impact of a dyadic exercise intervention including both groups as study participants remains to be determined. The authors review the current clinical evidence for dyadic exercise interventions, which are exercise regimens applied to both the person with dementia and the caregiver. A total of 4 controlled trials were reviewed. This review shows that dyadic exercise interventions are feasible and may produce a positive effect on functional independence and caregiver burden. However, there was insufficient evidence to support a benefit of dyadic exercise intervention on cognitive performance and on behavioral and neuropsychiatric symptoms in participants with dementia due to AD. A dyadic exercise intervention improves functional independence and caregiver burden. However, there is a need for well-designed randomized controlled clinical trials to confirm these benefits and to investigate several important points such as the effects of a dyadic exercise intervention on cognitive and noncognitive outcomes of AD, the optimal intensity of exercise training, and the cost effectiveness of such a program.

[Which hip articulation bearing for which patient? : Tribology of the future].

PubMed

Morlock, M M; Bishop, N; Kaddick, C

2011-12-01

Replacement of the hip joint has become an exceptionally successful procedure since the inauguration of the low friction principle by Charnley. Aseptic osteolysis and joint dislocation have been addressed by the development of wear-optimized materials and the introduction of larger heads. As an increase in head diameter against polyethylene causes wear increase, larger hard-on-hard bearings were introduced, which exhibit reduced wear and reduced dislocation risk with increasing head diameter. These findings were derived from standard simulator testing, not sufficiently considering the risk of fluid film breakdown under adverse conditions, which can cause a dramatic increase in wear and friction proportional to the head diameter. Such adverse conditions can occur clinically in patients due to several factors and have caused the presently observed unexpected problems with these new designs. Standardized preclinical testing has to be viewed as a minimum requirement but certainly not as a guarantee for the clinical success of new materials and designs even if the testing is adapted to the current patient requirements, which is presently not the case. The future of tribology lies in the prevention of adverse conditions in patients, the improvement and optimized use of proven existing materials and not in the use of new materials.

Next generation sequencing applications for breast cancer research

PubMed Central

PETRIC, ROXANA COJOCNEANU; POP, LAURA-ANCUTA; JURJ, ANCUTA; RADULY, LAJOS; DUMITRASCU, DAN; DRAGOS, NICOLAE; NEAGOE, IOANA BERINDAN

2015-01-01

For some time, cancer has not been thought of as a disease, but as a multifaceted, heterogeneous complex of genotypic and phenotypic manifestations leading to tumorigenesis. Due to recent technological progress, the outcome of cancer patients can be greatly improved by introducing in clinical practice the advantages brought about by the development of next generation sequencing techniques. Biomedical suppliers have come up with various applications which medical researchers can use to characterize a patient’s disease from molecular and genetic point of view in order to provide caregivers with rapid and relevant information to guide them in choosing the most appropriate course of treatment, with maximum efficiency and minimal side effects. Breast cancer, whose incidence has risen dramatically, is a good candidate for these novel diagnosis and therapeutic approaches, particularly when referring to specific sequencing panels which are designed to detect germline or somatic mutations in genes that are involved in breast cancer tumorigenesis and progression. Benchtop next generation sequencing machines are becoming a more common presence in the clinical setting, empowering physicians to better treat their patients, by offering early diagnosis alternatives, targeted remedies, and bringing medicine a step closer to achieving its ultimate goal, personalized therapy. PMID:26609257

Parkinson's disease (PD) in the elderly: an example of geriatric syndrome (GS)?

PubMed

Lauretani, Fulvio; Maggio, Marcello; Silvestrini, Claudio; Nardelli, Anna; Saccavini, Marsilio; Ceda, Gian Paolo

2012-01-01

PD is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. In the latest decade, the approach to PD was dramatically changed. In fact, although for many years PD has been considered only "a disease that affects walking", with a key role of the neurotransmitter dopamine, recently the neurological approach has been substantially modified. The approach for this disease is not only a neurological issue. Given the complexity of its clinical aspects, such as depression, anxiety, dementia, sleep disorder, pneumonia dysfagia-related and malnutrition, a multidisciplinary evaluation and not just a neurological evaluation is needed. We suggest a n multidisciplinary approach for this old actor, underlying a subtle link between neurophatological stages of the disease (Braak's classification) and clinical aspects (Braak's stages 1 and 2 associated with the premotor phase; Braak's stages 3-4 associated with the motor symptoms and Braak's stages 5-6 associated with cognitive impairment). In addition, we emphasize the usefulness of geriatric evaluation for the identification of frail "in situ", frail, and disable status for improving care and treatment in this multifaceted disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

The definition of insulin resistance using HOMA-IR for Americans of Mexican descent using machine learning.

PubMed

Qu, Hui-Qi; Li, Quan; Rentfro, Anne R; Fisher-Hoch, Susan P; McCormick, Joseph B

2011-01-01

The lack of standardized reference range for the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index has limited its clinical application. This study defines the reference range of HOMA-IR index in an adult Hispanic population based with machine learning methods. This study investigated a Hispanic population of 1854 adults, randomly selected on the basis of 2000 Census tract data in the city of Brownsville, Cameron County. Machine learning methods, support vector machine (SVM) and Bayesian Logistic Regression (BLR), were used to automatically identify measureable variables using standardized values that correlate with HOMA-IR; K-means clustering was then used to classify the individuals by insulin resistance. Our study showed that the best cutoff of HOMA-IR for identifying those with insulin resistance is 3.80. There are 39.1% individuals in this Hispanic population with HOMA-IR>3.80. Our results are dramatically different using the popular clinical cutoff of 2.60. The high sensitivity and specificity of HOMA-IR>3.80 for insulin resistance provide a critical fundamental for our further efforts to improve the public health of this Hispanic population.

The Definition of Insulin Resistance Using HOMA-IR for Americans of Mexican Descent Using Machine Learning

PubMed Central

Qu, Hui-Qi; Li, Quan; Rentfro, Anne R.; Fisher-Hoch, Susan P.; McCormick, Joseph B.

2011-01-01

Objective The lack of standardized reference range for the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index has limited its clinical application. This study defines the reference range of HOMA-IR index in an adult Hispanic population based with machine learning methods. Methods This study investigated a Hispanic population of 1854 adults, randomly selected on the basis of 2000 Census tract data in the city of Brownsville, Cameron County. Machine learning methods, support vector machine (SVM) and Bayesian Logistic Regression (BLR), were used to automatically identify measureable variables using standardized values that correlate with HOMA-IR; K-means clustering was then used to classify the individuals by insulin resistance. Results Our study showed that the best cutoff of HOMA-IR for identifying those with insulin resistance is 3.80. There are 39.1% individuals in this Hispanic population with HOMA-IR>3.80. Conclusions Our results are dramatically different using the popular clinical cutoff of 2.60. The high sensitivity and specificity of HOMA-IR>3.80 for insulin resistance provide a critical fundamental for our further efforts to improve the public health of this Hispanic population. PMID:21695082

Motion-gated acquisition for in vivo optical imaging

PubMed Central

Gioux, Sylvain; Ashitate, Yoshitomo; Hutteman, Merlijn; Frangioni, John V.

2009-01-01

Wide-field continuous wave fluorescence imaging, fluorescence lifetime imaging, frequency domain photon migration, and spatially modulated imaging have the potential to provide quantitative measurements in vivo. However, most of these techniques have not yet been successfully translated to the clinic due to challenging environmental constraints. In many circumstances, cardiac and respiratory motion greatly impair image quality and∕or quantitative processing. To address this fundamental problem, we have developed a low-cost, field-programmable gate array–based, hardware-only gating device that delivers a phase-locked acquisition window of arbitrary delay and width that is derived from an unlimited number of pseudo-periodic and nonperiodic input signals. All device features can be controlled manually or via USB serial commands. The working range of the device spans the extremes of mouse electrocardiogram (1000 beats per minute) to human respiration (4 breaths per minute), with timing resolution ⩽0.06%, and jitter ⩽0.008%, of the input signal period. We demonstrate the performance of the gating device, including dramatic improvements in quantitative measurements, in vitro using a motion simulator and in vivo using near-infrared fluorescence angiography of beating pig heart. This gating device should help to enable the clinical translation of promising new optical imaging technologies. PMID:20059276

Hepatitis A outbreak in Ba subdivision, Fiji, October–December 2013

PubMed Central

Rafai, Eric; Tolosa, Maria Ximena; Dawainavesi, Akanisi; Tabua, Anaseini Maisema; Tabua, Josefa

2015-01-01

Objective A cluster of suspected hepatitis A cases was notified to the Fiji Ministry of Health on 22 October 2013. An outbreak investigation team was mobilized to confirm the existence of an outbreak of hepatitis A and advise appropriate public health interventions. Methods A case definition for the outbreak investigation was established, and standardized data collection tools were used to collect information on clinical presentation and risk factors. An environmental assessment was also conducted. Results There were 160 clinical cases of hepatitis A of which 15 were laboratory-confirmed. The attack rate was 349 per 10 000 population in the Nukuloa nursing zone; there were no reported deaths. Residents of the Nukuloa settlement were 6.6 times more likely to present with symptomatic hepatitis A infection (95% confidence interval: 3.8–12.6) compared with residents of another village with a different water supply. Discussion This is the first significant hepatitis A outbreak documented in Ba subdivision and possibly in Fiji. Enhanced surveillance of hepatitis A may reveal other clusters in the country. Improving the primary water source dramatically reduced the occurance of disease in the affected community and adjacent areas. PMID:26306214

American surgery and the Affordable Care Act.

PubMed

Stain, Steven C; Hoyt, David B; Hunter, John G; Joyce, Geoffrey; Hiatt, Jonathan R

2014-09-01

The Affordable Care Act (ACA) attempts to change the way we finance and deliver health care by coordinating the delivery of primary, specialty, and hospital services in accountable care organizations. The ways in which accountable care organizations will develop and evolve is unclear; however, the effects on surgeons and their patients will be substantial. High-value care in the ACA emphasizes quality, safety, resource use and appropriateness, and the patient's experience of care. Payment will be linked to these principles. Department chairs overseeing a clinical enterprise in academic medical centers now must add financial and quality measures to the traditional missions of education, research, and clinical service. At a time when surgical training is in dramatic evolution, with work hour limitations for residents and an emphasis on quality, productivity, and increasing oversight of trainees for faculty, residency programs will need to meet the increasing demands of an aging population and newly insured patients under the ACA. The American College of Surgeons, with its century-long commitment to quality improvement, research-based standards, and performance measurement and verification, has begun its Inspiring Quality Campaign, is developing new educational tools, and is preparing proposals for payment reform based on surgeons' participation in quality programs.

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis.

PubMed

Shen, Jiayun; Shang, Qing; Tam, Lai-Shan

2016-01-01

Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Coaching of physicians by RNs to improve diabetes care.

PubMed

Frederick, Mary L; Johnson, Pamela Jo; Duffee, Janelle; McCarthy, Bruce D

2013-01-01

The purpose of this study is to describe preliminary results of an innovative quality improvement intervention focused on improving physician practice patterns in diabetes care via Coaching Physicians by RN certified diabetes educators (CDEs), a program called "CPR for Diabetes Care." METHODS The program identified primary care physicians with optimal diabetes control rates below the system aggregate (n = 195). Physicians with the lowest rates (n = 74) were targeted for comprehensive intervention. All other low-performing physicians practicing in the same clinic system (n = 121) comprised the comparison group. Data were obtained from electronic diabetes registries for 2007 and 2008. Each physician had a set of measures from 2 points in time. Measures included optimal diabetes scores and the 5 component measures of the optimal diabetes care bundle (A1C <7, low-density lipoprotein cholesterol <100, blood pressure <130/80, aspirin use if older than 40, and no tobacco use). T tests and difference-in-difference models were used to examine changes over time. Optimal diabetes scores increased 11.7 points (from 14.7% to 26.4%) for intervention physicians and 4.0 points (from 29.7% to 32.9%) for comparison physicians. The improvement was greater for the intervention group. The greatest component improvements were in control of blood pressure and cholesterol. CONCLUSIONS Coaching low-performing physicians dramatically improved the proportion of diabetes patients with optimal diabetes control. The CPR for Diabetes Care program represents an innovative and effective way to address the long-standing problem of disseminating and sustaining quality improvement efforts by focusing on low-performing physicians.

Readability of Patient Education Materials in Hand Surgery and Health Literacy Best Practices for Improvement.

PubMed

Hadden, Kristie; Prince, Latrina Y; Schnaekel, Asa; Couch, Cory G; Stephenson, John M; Wyrick, Theresa O

2016-08-01

This study aimed to update a portion of a 2008 study of patient education materials from the American Society for Surgery of the Hand Web site with new readability results, to compare the results to health literacy best practices, and to make recommendations to the field for improvement. A sample of 77 patient education documents were downloaded from the American Society for Surgery of the Hand Web site, handcare.org, and assessed for readability using 4 readability tools. Mean readability grade-level scores were derived. Best practices for plain language for written health materials were compiled from 3 government agency sources. The mean readability of the 77 patient education documents in the study was 9.3 grade level. This reading level is reduced from the previous study in 2008 in which the overall mean was 10.6; however, the current sample grade level still exceeds recommended readability according to best practices. Despite a small body of literature on the readability of patient education materials related to hand surgery and other orthopedic issues over the last 7 years, readability was not dramatically improved in our current sample. Using health literacy as a framework, improvements in hand surgery patient education may result in better understanding and better outcomes for patients seeing hand surgeons. Improved understanding of patient education materials related to hand surgery may improve preventable negative outcomes that are clinically significant as well as contribute to improved quality of life for patients. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Dissecting the determinants of depressive disorders outcome: an in depth analysis of two clinical cases

PubMed Central

Serretti, Alessandro; Calati, Raffaella; Oasi, Osmano; De Ronchi, Diana; Colombo, Cristina

2007-01-01

Clinicians face everyday the complexity of depression. Available pharmacotherapies and psychotherapies improve patients suffering in a large part of subjects, however up to half of patients do not respond to treatment. Clinicians may forecast to a good extent if a given patient will respond or not, based on a number of data and sensations that emerge from face to face assessment. Conversely, clinical predictors of non response emerging from literature are largely unsatisfactory. Here we try to fill this gap, suggesting a comprehensive assessment of patients that may overcome the limitation of standardized assessments and detecting the factors that plausibly contribute to so marked differences in depressive disorders outcome. For this aim we present and discuss two clinical cases. Mr. A was an industrial manager who came to psychiatric evaluation with a severe depressive episode. His employment was demanding and the depressive episode undermined his capacity to manage it. Based on standardized assessment, Mr. A condition appeared severe and potentially dramatic. Mrs. B was a housewife who came to psychiatric evaluation with a moderate depressive episode. Literature predictors would suggest Mrs. B state as associated with a more favourable outcome. However the clinician impression was not converging with the standardized assessment and in fact the outcome will reverse the prediction based on the initial formal standard evaluation. Although the present report is based on two clinical cases and no generalizability is possible, a more detailed analysis of personality, temperament, defense mechanisms, self esteem, intelligence and social adjustment may allow to formalize the clinical impressions used by clinicians for biologic and pharmacologic studies. PMID:17286859

The changing face of chronic illness management in primary care: a qualitative study of underlying influences and unintended outcomes.

PubMed

Hunt, Linda M; Kreiner, Meta; Brody, Howard

2012-01-01

Recently, there has been dramatic increase in the diagnosis and pharmaceutical management of common chronic illnesses. Using qualitative data collected in primary care clinics, we assessed how these trends play out in clinical care. This qualitative study focused on management of type 2 diabetes and hypertension in 44 primary care clinics in Michigan and was based on interviews with 58 clinicians and 70 of their patients, and observations of 107 clinical consultations. We assessed clinicians' treatment strategies and discussions of factors influencing treatment decisions, and patients' understandings and experiences in managing these illnesses. Clinicians focused on helping patients achieve test results recommended by national guidelines, and most reported combining 2 or more medications per condition to reach targets. Medication selection and management was the central focus of the consultations we observed. Polypharmacy was common among patients, with more than one-half taking 5 or more medications. Patient interviews indicated that heavy reliance on pharmaceuticals presents challenges to patient well-being, including financial costs and experiences of adverse health effects. Factors promoting heavy use of pharmaceuticals include lower diagnostic and treatment thresholds, clinician-auditing and reward systems, and the prescribing cascade, whereby more medications are prescribed to control the effects of already-prescribed medications. We present a conceptual model, the inverse benefit law, to provide insight into the impact of pharmaceutical marketing efforts on the observed trends. We make recommendations about limiting the influence of the pharmaceutical industry on clinical practice, toward improving the well-being of patients with chronic illness.

Research Review: Gender identity in youth: treatment paradigms and controversies.

PubMed

Turban, Jack L; Ehrensaft, Diane

2017-10-26

Pediatric gender identity has gained increased attention over the past several years in the popular media, political arena, and medical literature. This article reviews terminology in this evolving field, traditional models of gender identity development and their limitations, epidemiology and natural history of cross-gender identification among children and adolescents, co-occurring conditions and behaviors, research into the biological and psychosocial determinants of cross-gender identification, and research into the options regarding and benefits of clinical approaches to gender incongruent youth. Based on a critical review of the extant literature, both theoretical and empirical, that addresses the issue of pediatric gender identity, the authors synthesized what is presently known and what is in need of further research in order to elucidate the developmental trajectory and clinical needs of gender diverse youth. The field of pediatric gender identity has evolved substantially over the past several years. New research suggests that cross-gender identification is prevalent (approximately 1% of youth). These youth suffer disproportionately high rates of anxiety, depression, and suicidality. Although research into the etiology of cross-gender identification is limited, emerging data have shown that affirmative treatment protocols may improve the high rates of mental health difficulties seen among these patients. The field of pediatric gender identity has evolved dramatically. Emerging data suggest that these patients' high rates of anxiety, depression, and suicidality appear to be improved with affirmative protocols, although future longitudinal data are needed. © 2017 Association for Child and Adolescent Mental Health.

[Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].

PubMed

Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie

2013-02-01

To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

The cost-effectiveness of training US primary care physicians to conduct colorectal cancer screening in family medicine residency programs.

PubMed

Edwardson, Nicholas; Bolin, Jane N; McClellan, David A; Nash, Philip P; Helduser, Janet W

2016-04-01

Demand for a wide array of colorectal cancer screening strategies continues to outpace supply. One strategy to reduce this deficit is to dramatically increase the number of primary care physicians who are trained and supportive of performing office-based colonoscopies or flexible sigmoidoscopies. This study evaluates the clinical and economic implications of training primary care physicians via family medicine residency programs to offer colorectal cancer screening services as an in-office procedure. Using previously established clinical and economic assumptions from existing literature and budget data from a local grant (2013), incremental cost-effectiveness ratios are calculated that incorporate the costs of a proposed national training program and subsequent improvements in patient compliance. Sensitivity analyses are also conducted. Baseline assumptions suggest that the intervention would produce 2394 newly trained residents who could perform 71,820 additional colonoscopies or 119,700 additional flexible sigmoidoscopies after ten years. Despite high costs associated with the national training program, incremental cost-effectiveness ratios remain well below standard willingness-to-pay thresholds under base case assumptions. Interestingly, the status quo hierarchy of preferred screening strategies is disrupted by the proposed intervention. A national overhaul of family medicine residency programs offering training for colorectal cancer screening yields satisfactory incremental cost-effectiveness ratios. However, the model places high expectations on primary care physicians to improve current compliance levels in the US. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-muscle electrical stimulation and stand training: Effects on standing.

PubMed

Momeni, Kamyar; Ramanujam, Arvind; Garbarini, Erica L; Forrest, Gail F

2018-02-15

To examine the biomechanical and neuromuscular effects of a longitudinal multi-muscle electrical stimulation (submaximal intensities) training of the lower limbs combined with/without activity-based stand training, on the recovery of stability and function for one individual with spinal cord injury (SCI). Single-subject, longitudinal study. Neuroplasticity laboratory. A 34-year-old male, with sensory- and motor-complete SCI (C5/C6). Two consecutive interventions: 61 hours of supine, lower-limb ES (ES-alone) and 51 hours of ES combined with stand training using an overhead body-weight support system (ST + ES). Clinical measures, trunk stability, and muscle activity were assessed and compared across time points. Trunk Stability Limit (TSL) determined improvements in trunk independence. Functional clinical values increased after both interventions, with further increases post ST + ES. Post ES-alone, trunk stability was maintained at 81% body-weight (BW) loading before failure; post ST + ES, BW loading increased to 95%. TSL values decreased post ST + ES (TSL A/P =54.0 kg.cm, TSL M/L =14.5 kg.cm), compared to ES-alone (TSL A/P =8.5 kg.cm, TSL M/L =3.9 kg.cm). Trunk muscle activity decreased post ST + ES training, compared to ES-alone. Neuromuscular and postural trunk control dramatically improved following the multi-muscle ES of the lower limbs with stand training. Multi-muscle ES training paradigm of the lower limb, using traditional parameters, may contribute to the functional recovery of the trunk.

Auditory midbrain implant: a review.

PubMed

Lim, Hubert H; Lenarz, Minoo; Lenarz, Thomas

2009-09-01

The auditory midbrain implant (AMI) is a new hearing prosthesis designed for stimulation of the inferior colliculus in deaf patients who cannot sufficiently benefit from cochlear implants. The authors have begun clinical trials in which five patients have been implanted with a single shank AMI array (20 electrodes). The goal of this review is to summarize the development and research that has led to the translation of the AMI from a concept into the first patients. This study presents the rationale and design concept for the AMI as well a summary of the animal safety and feasibility studies that were required for clinical approval. The authors also present the initial surgical, psychophysical, and speech results from the first three implanted patients. Overall, the results have been encouraging in terms of the safety and functionality of the implant. All patients obtain improvements in hearing capabilities on a daily basis. However, performance varies dramatically across patients depending on the implant location within the midbrain with the best performer still not able to achieve open set speech perception without lip-reading cues. Stimulation of the auditory midbrain provides a wide range of level, spectral, and temporal cues, all of which are important for speech understanding, but they do not appear to sufficiently fuse together to enable open set speech perception with the currently used stimulation strategies. Finally, several issues and hypotheses for why current patients obtain limited speech perception along with several feasible solutions for improving AMI implementation are presented.

Diabetic Macular Edema: Options for Adjunct Therapy.

PubMed

Calvo, Pilar; Abadia, Beatriz; Ferreras, Antonio; Ruiz-Moreno, Oscar; Verdes, Guayente; Pablo, Luis E

2015-09-01

Diabetes mellitus (DM) is a chronic disease that affects 387 million people worldwide. Diabetic retinopathy (DR), a common complication of DM, is the main cause of blindness in the active population. Diabetic macular edema (DME) may occur at any stage of DR, and is characterized by vascular hyperpermeability accompanied by hard exudates within the macula. Medical and surgical therapies have dramatically reduced the progression of DR, and timely intervention can reduce the risk of severe vision loss by more than 90 %. In 2012, intravitreal ranibizumab became the first antivascular endothelial growth factor (anti-VEGF) agent approved for DME and, since then, many reports of the use of ranibizumab for DME have been promising. Randomized, prospective, multicenter clinical trials-most notably, RESOLVE, READ-2, RISE/RIDE, RESTORE, DRCR.net protocol I, and RETAIN-reported improvements in best-corrected visual acuity and decreased central retinal thickness as measured with optical coherence tomography in patients with DME. Similar treatment benefits have also been noted in clinical trials evaluating intravitreal aflibercept and bevacizumab (DAVINCI, VISTA/VIVID, and BOLT) and more recently DRCR.net protocol T. Intravitreal steroids (dexamethasone intravitreal implant and fluocinolone acetonide), particularly in refractory cases, also play a significant role in the management of DME (MEAD/CHAMPLAIN and FAMOUS/FAME studies). In summary, over the last 5 years, blocking VEGF and inflammation has been shown to improve visual outcomes in patients with macular edema due to DM, revolutionizing the treatment of center-involved DME and establishing a new standard of care.

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care.

PubMed

Cherry, Simon R; Jones, Terry; Karp, Joel S; Qi, Jinyi; Moses, William W; Badawi, Ramsey D

2018-01-01

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Novel methods of imaging and analysis for the thermoregulatory sweat test.

PubMed

Carroll, Michael Sean; Reed, David W; Kuntz, Nancy L; Weese-Mayer, Debra Ellyn

2018-06-07

The thermoregulatory sweat test (TST) can be central to the identification and management of disorders affecting sudomotor function and small sensory and autonomic nerve fibers, but the cumbersome nature of the standard testing protocol has prevented its widespread adoption. A high resolution, quantitative, clean and simple assay of sweating could significantly improve identification and management of these disorders. Images from 89 clinical TSTs were analyzed retrospectively using two novel techniques. First, using the standard indicator powder, skin surface sweat distributions were determined algorithmically for each patient. Second, a fundamentally novel method using thermal imaging of forced evaporative cooling was evaluated through comparison with the standard technique. Correlation and receiver operating characteristic analyses were used to determine the degree of match between these methods, and the potential limits of thermal imaging were examined through cumulative analysis of all studied patients. Algorithmic encoding of sweating and non-sweating regions produces a more objective analysis for clinical decision making. Additionally, results from the forced cooling method correspond well with those from indicator powder imaging, with a correlation across spatial regions of -0.78 (CI: -0.84 to -0.71). The method works similarly across body regions, and frame-by-frame analysis suggests the ability to identify sweating regions within about 1 second of imaging. While algorithmic encoding can enhance the standard sweat testing protocol, thermal imaging with forced evaporative cooling can dramatically improve the TST by making it less time-consuming and more patient-friendly than the current approach.

Redesign of a university hospital preanesthesia evaluation clinic using a queuing theory approach.

PubMed

Zonderland, Maartje E; Boer, Fredrik; Boucherie, Richard J; de Roode, Annemiek; van Kleef, Jack W

2009-11-01

Changes in patient length of stay (the duration of 1 clinic visit) as a result of the introduction of an electronic patient file system forced an anesthesia department to change its outpatient clinic organization. In this study, we sought to demonstrate how the involvement of essential employees combined with mathematical techniques to support the decision-making process resulted in a successful intervention. The setting is the preanesthesia evaluation clinic (PAC) of a university hospital, where patients consult several medical professionals, either by walk-in or appointment. Queuing theory was used to model the initial set-up of the clinic, and later to model possible alternative designs. With the queuing model, possible improvements in efficiency could be investigated. Inputs to the model were patient arrival rates and expected service times with clinic employees, collected from the clinic's logging system and by observation. The performance measures calculated with the model were patient length of stay and employee utilization rate. Supported by the model outcomes, a working group consisting of representatives of all clinic employees decided whether the initial design should be maintained or an intervention was needed. The queuing model predicted that 3 of the proposed alternatives would result in better performance. Key points in the intervention were the rescheduling of appointments and the reallocation of tasks. The intervention resulted in a shortening of the time the anesthesiologist needed to decide upon approving the patient for surgery. Patient arrivals increased sharply over 1 yr by more than 16%; however, patient length of stay at the clinic remained essentially unchanged. If the initial set-up of the clinic would have been maintained, the patient length of stay would have increased dramatically. Queuing theory provides robust methods to evaluate alternative designs for the organization of PACs. In this article, we show that queuing modeling is an adequate approach for redesigning processes in PACs.

Acute hemorrhagic edema of infancy: report of three cases.

PubMed

Emerich, Paulo Sergio; Prebianchi, Patricia Almeida; Motta, Luciene Lage da; Lucas, Elton Almeida; Ferreira, Leonardo Mello

2011-01-01

Acute Hemorrhagic Edema of Infancy is an infrequent leukocytoclastic vasculitis which occurs almost exclusively in children between 4 months and 2 years of age. It is clinically characterized by the triad fever, purpuric lesions on the face, auricular pinna and extremities, and edema. Although the cutaneous findings are dramatic and of rapid onset, the prognosis is favorable, with spontaneous resolution within 1 to 3 weeks. Three cases are described in which clinical and histopathological findings are characteristic of acute hemorrhagic edema of infancy.

Achieving appropriate design for developing world heath care: the case of a low-cost autoclave for primary health clinics.

PubMed

Cho, Hallie S; Tao, Gregory D; Winter, Amos

2012-01-01

In developing world health clinics, incidence of surgical site infection is 2 to 10 times higher than in developed world hospitals. This paper identifies lack of availability of appropriately designed, low-cost autoclaves in developing world health clinics as a major contributing factor to the dramatic gap in surgical site infection rates. The paper describes the process of developing a low-cost autoclave that addresses the unique challenges faced by developing world primary health clinics and discusses how appropriateness of design was determined. The resulting pressure cooker-based autoclave design was fabricated and tested against the CDC specifications. Twelve partnering clinics in Nepal trialed these autoclaves from July until December 2012.

Breast ultrasound tomography: bridging the gap to clinical practice

NASA Astrophysics Data System (ADS)

Duric, Neb; Littrup, Peter; Li, Cuiping; Roy, Olivier; Schmidt, Steven; Janer, Roman; Cheng, Xiaoyang; Goll, Jeffrey; Rama, Olsi; Bey-Knight, Lisa; Greenway, William

2012-03-01

Conventional sonography, which performs well in dense breast tissue and is comfortable and radiation-free, is not practical for screening because of its operator dependence and the time needed to scan the whole breast. While magnetic resonance imaging (MRI) can significantly improve on these limitations, it is also not practical because it has long been prohibitively expensive for routine use. There is therefore a need for an alternative breast imaging method that obviates the constraints of these standard imaging modalities. The lack of such an alternative is a barrier to dramatically impacting mortality (about 45,000 women in the US per year) and morbidity from breast cancer because, currently, there is a trade-off between the cost effectiveness of mammography and sonography on the one hand and the imaging accuracy of MRI on the other. This paper presents a progress report on our long term goal to eliminate this trade-off and thereby improve breast cancer survival rates and decrease unnecessary biopsies through the introduction of safe, cost-effective, operatorindependent sonography that can rival MRI in accuracy. The objective of the study described in this paper was to design and build an improved ultrasound tomography (UST) scanner in support of our goals. To that end, we report on a design that builds on our current research prototype. The design of the new scanner is based on a comparison of the capabilities of our existing prototype and the performance needed for clinical efficacy. The performance gap was quantified by using clinical studies to establish the baseline performance of the research prototype, and using known MRI capabilities to establish the required performance. Simulation software was used to determine the basic operating characteristics of an improved scanner that would provide the necessary performance. Design elements focused on transducer geometry, which in turn drove the data acquisition system and the image reconstruction engine specifications. The feasibility of UST established by our earlier work and that of other groups, forms the rationale for developing a UST system that has the potential to become a practical, low-cost device for breast cancer screening and diagnosis.

Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model.

PubMed

Ay, Hakan; Arsava, E Murat; Johnston, S Claiborne; Vangel, Mark; Schwamm, Lee H; Furie, Karen L; Koroshetz, Walter J; Sorensen, A Gregory

2009-01-01

Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >/=4) as covariates. Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >/=4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.

Enhanced Performance of Recycled Aggregate Concrete with Atomic Polymer Technology

DOT National Transportation Integrated Search

2012-06-01

The atomic polymer technology in form of mesoporous inorganic polymer (MIP) can effectively improve material durability and performance of concrete by dramatically increase inter/intragranular bond strength of concrete at nano-scale. The strategy of ...

The Fundamental Re-Thinking and Redesign of the Military Pay Document Processing System.

DTIC Science & Technology

1999-03-01

the Army and Coast Guard’s MPDP can be dramatically improved by eliminating middlemen functions (PAC and finance office) and shortening the value chain using IT along with other transformation enablers.

Liven up Your Student Dramatics with Commedia dell' Arte.

ERIC Educational Resources Information Center

Potter, Jonathan

1980-01-01

Suggests using the ancient Commedia dell' Arte technique of establishing characters and a plot and then allowing the actors to create their own play. Indicates that this improves student performances even in more traditional plays. (TJ)

NREL Discovers Enzyme Domains that Dramatically Improve Performance | News

Science.gov Websites

seven years of thorough experimental work to develop the tools needed to ascertain that there are a . It was the melding of experimental biochemistry and computational science that brought this study to

Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design

PubMed Central

Qian, Jing; T.Hyman, Bradley; Betensky, Rebecca A.

2017-01-01

Importance The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. Objective To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. Design, Setting, and Participants A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging’s Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. Main Outcomes and Measures We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Results Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = −0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P < .001) and lower logical memory score (β = −1.07; P = .005). The rate of change of the clinical and cognitive scores varied depending on Braak stage, when adjusting for plaques, age of death, sex, education, and APOE genotype. For example, comparing high vs low Braak stage with other variables fixed, the logical memory score decreased a substantial 0.38 additional units per year (95% CI, −0.70 to −0.06; P = .02). Using these data, we estimate that a 300-participant clinical trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89% power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage had not used for eligibility. Conclusions and Relevance We found that knowledge of neurofibrillary tangle stage, modeled as the sort of information that could be available from tau positron-emission tomography scans and its use to determine eligibility to a trial, could dramatically improve the power of clinical trials and equivalently reduce the required sample sizes of clinical trials. PMID:28288263

Recent Advances in Nanotechnology for Diabetes Treatment

PubMed Central

DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

2015-01-01

Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955

Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy.

PubMed

Briani, Chiara; Manara, Renzo; Lessi, Federica; Citton, Valentina; Zambello, Renato; Adami, Fausto

2012-05-01

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease

Modular Chemical Process Intensification: A Review.

PubMed

Kim, Yong-Ha; Park, Lydia K; Yiacoumi, Sotira; Tsouris, Costas

2017-06-07

Modular chemical process intensification can dramatically improve energy and process efficiencies of chemical processes through enhanced mass and heat transfer, application of external force fields, enhanced driving forces, and combinations of different unit operations, such as reaction and separation, in single-process equipment. These dramatic improvements lead to several benefits such as compactness or small footprint, energy and cost savings, enhanced safety, less waste production, and higher product quality. Because of these benefits, process intensification can play a major role in industrial and manufacturing sectors, including chemical, pulp and paper, energy, critical materials, and water treatment, among others. This article provides an overview of process intensification, including definitions, principles, tools, and possible applications, with the objective to contribute to the future development and potential applications of modular chemical process intensification in industrial and manufacturing sectors. Drivers and barriers contributing to the advancement of process intensification technologies are discussed.

Electrical properties of zinc-oxide-based thin-film transistors using strontium-oxide-doped semiconductors

NASA Astrophysics Data System (ADS)

Wu, Shao-Hang; Zhang, Nan; Hu, Yong-Sheng; Chen, Hong; Jiang, Da-Peng; Liu, Xing-Yuan

2015-10-01

Strontium-zinc-oxide (SrZnO) films forming the semiconductor layers of thin-film transistors (TFTs) are deposited by using ion-assisted electron beam evaporation. Using strontium-oxide-doped semiconductors, the off-state current can be dramatically reduced by three orders of magnitude. This dramatic improvement is attributed to the incorporation of strontium, which suppresses carrier generation, thereby improving the TFT. Additionally, the presence of strontium inhibits the formation of zinc oxide (ZnO) with the hexagonal wurtzite phase and permits the formation of an unusual phase of ZnO, thus significantly changing the surface morphology of ZnO and effectively reducing the trap density of the channel. Project supported by the National Natural Science Foundation of China (Grant No. 6140031454) and the Innovation Program of Chinese Academy of Sciences and State Key Laboratory of Luminescence and Applications.

Directed evolution of an ultrastable carbonic anhydrase for highly efficient carbon capture from flue gas

DOE PAGES

Alvizo, Oscar; Nguyen, Luan J.; Savile, Christopher K.; ...

2014-11-03

Carbonic anhydrase (CA) is one of nature’s fastest enzymes and can dramatically improve the economics of carbon capture under demanding environments such as coal-fired power plants. The use of CA to accelerate carbon capture is limited by the enzyme’s sensitivity to the harsh process conditions. Using directed evolution, the properties of a β-class CA from Desulfovibrio vulgaris were dramatically enhanced. Iterative rounds of library design, library generation, and high-throughput screening identified highly stable CA variants that tolerate temperatures of up to 107 °C in the presence of 4.2 M alkaline amine solvent at pH >10.0. This increase in thermostability andmore » alkali tolerance translates to a 4,000,000-fold improvement over the natural enzyme. In conclusion, at pilot scale, the evolved catalyst enhanced the rate of CO2 absorption 25-fold compared with the noncatalyzed reaction.« less

Modular Chemical Process Intensification: A Review

DOE PAGES

Kim, Yong-ha; Park, Lydia K.; Yiacoumi, Sotira; ...

2016-06-24

Modular chemical process intensification can dramatically improve energy and process efficiencies of chemical processes through enhanced mass and heat transfer, application of external force fields, enhanced driving forces, and combinations of different unit operations, such as reaction and separation, in single-process equipment. Dramatic improvements such as these lead to several benefits such as compactness or small footprint, energy and cost savings, enhanced safety, less waste production, and higher product quality. Because of these benefits, process intensification can play a major role in industrial and manufacturing sectors, including chemical, pulp and paper, energy, critical materials, and water treatment, among others. Thismore » article provides an overview of process intensification, including definitions, principles, tools, and possible applications, with the objective to contribute to the future development and potential applications of modular chemical process intensification in industrial and manufacturing sectors. Drivers and barriers contributing to the advancement of process intensification technologies are discussed.« less

Directed evolution of an ultrastable carbonic anhydrase for highly efficient carbon capture from flue gas

PubMed Central

Alvizo, Oscar; Nguyen, Luan J.; Savile, Christopher K.; Bresson, Jamie A.; Lakhapatri, Satish L.; Solis, Earl O. P.; Fox, Richard J.; Broering, James M.; Benoit, Michael R.; Zimmerman, Sabrina A.; Novick, Scott J.; Liang, Jack; Lalonde, James J.

2014-01-01

Carbonic anhydrase (CA) is one of nature’s fastest enzymes and can dramatically improve the economics of carbon capture under demanding environments such as coal-fired power plants. The use of CA to accelerate carbon capture is limited by the enzyme’s sensitivity to the harsh process conditions. Using directed evolution, the properties of a β-class CA from Desulfovibrio vulgaris were dramatically enhanced. Iterative rounds of library design, library generation, and high-throughput screening identified highly stable CA variants that tolerate temperatures of up to 107 °C in the presence of 4.2 M alkaline amine solvent at pH >10.0. This increase in thermostability and alkali tolerance translates to a 4,000,000-fold improvement over the natural enzyme. At pilot scale, the evolved catalyst enhanced the rate of CO2 absorption 25-fold compared with the noncatalyzed reaction. PMID:25368146

Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions

PubMed Central

Kazama, Itsuro; Miura, Chieko; Nakajima, Toshiyuki

2016-01-01

Case series Patient: Female, 24 • Male, 35 Final Diagnosis: EBV-induced infectious mononucleosis Symptoms: Fever • general malaise • lymphadenopathy Medication: — Clinical Procedure: Physical examination and serological testing Specialty: Infectious diseases Objective: Rare co-existance of disease or pathology Background: Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus (EBV) infection. In adults, the symptoms can often be severe and prolonged, sometimes causing serious complications. Analgesic or antipyretic drugs are normally used to relieve the symptoms. However, there is no causal treatment for the disease. Case Report: Two cases of adult patients with atopic predispositions developed nocturnal fever, general fatigue, pharyngitis and lymphadenopathy after an exacerbation of atopic symptoms or those of allergic rhinitis. Due to the positive results for EBV viral-capsid antigen (VCA) IgM and negative results for EBV nuclear antigen (EBNA) IgG, diagnoses of infectious mononucleosis induced by EBV were made in both cases. Although oral antibiotics or acetaminophen alone did not improve the deteriorating symptoms, including fever, headache and general fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs), such as tiaramide or loxoprofen, completely improved the symptoms quickly after the initiation. Conclusions: In these cases, given the atopic predispositions of the patients, an enhanced immunological response was likely to be mainly responsible for the pathogenesis of the symptoms. In such cases, NSAIDs, that are known to reduce the activity of EBV, may dramatically improve the deteriorating symptoms quickly after the initiation. In the present cases, the immunosuppressive property of these drugs was considered to suppress the activity of lymphocytes and thus provide the rapid and persistent remission of the disease. PMID:26874639

Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.

PubMed

Marzo-Ortega, Helena; McGonagle, Dennis; Rhodes, Laura A; Tan, Ai Lyn; Conaghan, Philip G; O'Connor, Philip; Tanner, Steven F; Fraser, Alexander; Veale, Douglas; Emery, Paul

2007-06-01

Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. To assess the impact of infliximab on bone oedema in PsA as shown by MRI. 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.

Current status of device-assisted enteroscopy: Technical matters, indication, limits and complications

PubMed Central

Riccioni, Maria Elena; Urgesi, Riccardo; Cianci, Rossella; Bizzotto, Alessandra; Galasso, Domenico; Costamagna, Guido

2012-01-01

Enteroscopy, defined as direct visualization of the small bowel with the use of a fiberoptic or capsule endoscopy, has progressed considerably over the past several years. The need for endoscopic access to improve diagnosis and treatment of small bowel disease has led to the development of novel technologies one of which is non-invasive, the video capsule, and a type of invasive technique, the device-assisted enteroscopy. In particular, the device-assisted enteroscopy consists then of three different types of instruments all able to allow, in skilled hands, to display partially or throughout its extension (if necessary) the small intestine. Newer devices, double balloon, single balloon and spiral endoscopy, are just entering clinical use. The aim of this article is to review recent advances in small bowel enteroscopy, focusing on indications, modifications to improve imaging and techniques, pitfalls, and clinical applications of the new instruments. With new technologies, the trials and tribulations of learning new endoscopic skills and determining their role in the diagnosis and treatment of small bowel disease come. Identification of small bowel lesions has dramatically improved. Studies are underway to determine the best strategy to apply new enteroscopy technologies for the diagnosis and management of small bowel disease, particularly obscure bleeding. Vascular malformations such as angiectasis and small bowel neoplasms as adenocarcinoma or gastrointestinal stromal tumors. Complete enteroscopy of the small bowel is now possible. However, because of the length of the small bowel, endoscopic examination and therapeutic maneuvers require significant skill, radiological assistance, the use of deep sedation with the assistance of the anesthetist. Prospective randomized studies are needed to guide diagnostic testing and therapy with these new endoscopic techniques. PMID:23189216

HER2-family signalling mechanisms, clinical implications and targeting in breast cancer.

PubMed

Elster, N; Collins, D M; Toomey, S; Crown, J; Eustace, A J; Hennessy, B T

2015-01-01

Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC.

Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for achalasia: results of a randomised clinical trial.

PubMed

Kumagai, Koshi; Kjellin, Ann; Tsai, Jon A; Thorell, Anders; Granqvist, Staffan; Lundell, Lars; Håkanson, Bengt

2014-01-01

The optimal anti-reflux procedure after Heller cardiomyotomy for oesophageal achalasia remains unclear. The most commonly used procedure is the anterior partial fundoplication according to Dor, although during recent years the posterior counterpart (Toupet) has become popular. Patients with newly diagnosed achalasia and referred for cardiomyotomy were randomised to receive either an anterior or partial posterior fundoplication following a classical cardiomyotomy. The effect of surgery was assessed during the first postoperative year by Eckardt scores, EORTC QLQ-OES18 scores and HRQL questionnaires. Timed barium oesophagogram (TBO) and ambulatory 24-h pH monitoring were performed to determine oesophageal emptying and the degree of reflux control, respectively. Forty-two patients were randomised into Dor (n = 20) and Toupet (n = 22) groups. Eckardt scores improved dramatically with both procedures, but the EORTC QLQ-OES18 (functional scales) scores revealed significantly better relative improvements in the Toupet group compared to the Dor repair (P = 0.044). Corresponding advantages in favour of Toupet were observed postoperatively in the percentage of oesophageal emptying at TBO (P = 0.011 in height and P = 0.018 in area), an effect not observed in the Dor group. There were no other significant differences recorded between the study groups concerning HRQL evaluations and objective assessment of gastro-oesophageal acid reflux. A partial posterior fundoplication after cardiomyotomy seems to achieve more improvement in oesophageal emptying and EORTC QLQ-OES18 functional scale scores than the anterior fundoplication. Otherwise no differences between the two anti-reflux repairs were noted. ClinicalTrials.gov Identifier: NCT01933373. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Improving cost-effectiveness of and outcomes from drug therapy in patients with atrial fibrillation in managed care: role of the pharmacist.

PubMed

Johnson, Samuel G

2009-08-01

The medical care costs for procedures, medications, and testing associated with atrial fibrillation (AF) in the United States are high and projected to increase markedly in the future as the number of Americans affected grows. The burden on patient quality of life, the health care system, and society are pharmacoeconomic considerations in managing AF. To identify key pharmacoeconomic considerations in managing AF and describe ways in which managed care pharmacists can improve the cost-effectiveness of and outcomes from drug therapy for AF. The high medical care costs of AF are largely the result of the high cost of hospitalization and inpatient procedures. Recurrence of AF dramatically increases costs, especially for hospital care. Managed care pharmacists have many opportunities to provide cost-effective care to and improve outcomes in patients with AF. Policy and process review, population management, and case management are key strategies for improving outcomes in patients with AF. Pharmacist input into policy and process review, including pharmacy benefits design, formulary management, and the use of information technology, can help ensure that the use of drug therapy for AF is cost-effective. Population management strategies, such as development of clinical pathways and patient registries, seek to improve the quality, consistency, and cost-effectiveness of care and the likelihood that desired therapeutic outcomes are achieved through targeted interventions. Case management strategies focus on longitudinal care for individuals in order to improve quality. Pharmacist-managed anticoagulation services and antiarrhythmic drug monitoring are the 2 most widely known case management strategies for patients with AF. Managed care pharmacists can screen patients with AF for the use of anticoagulation, which is needed to prevent embolic stroke but is under-used, even though recommended by evidence-based guidelines. The clinical efficacy and cost-effectiveness of pharmacist-managed anticoagulation services for patients with AF are well documented. Pharmacist-managed antiarrhythmic drug monitoring is a less well-known case management strategy that facilitates early detection and intervention to minimize toxicity. Managed care pharmacists can play an instrumental role in implementing strategies to improve the cost-effectiveness of and outcomes from drug therapy for AF.

Perfect Mirror Design Technology

DTIC Science & Technology

1999-02-01

with Prof. Mario Molina, recipient of the 1995 Nobel Prize in Chemistry. The partnership, along with Aerodyne Research Inc., looked at how sulfur...Corporation is developing standards for nondestructive evaluation ( NDE ) techniques for industry use. Use of the new standards will result in improved...novel testing methodology that dramatically improves the accuracy of NDE techniques used to detect flaws. Basic Research Five years ago, the main

Exploiting trait correlations for next-generation grain yield and end-use quality improvement of U.S. hard winter wheat

USDA-ARS?s Scientific Manuscript database

Since the early 1980s, the land area planted to U.S. hard winter wheat and the share of U.S. wheat in global export markets have both declined dramatically. Improved profitability of other crops relative to wheat, declining or static domestic wheat flour consumption, and an increasingly competitive ...

Intensive hardwood log bucker training using HW Buck dramatically improves value recovery

Treesearch

James B. Pickens; Aaron Everett; Scott Noble; John E. Baumgras; Philip A. Araman; Conrad Waniger; Al Steele

2006-01-01

It has long been recognized that inappropriate placement of crosscuts when manufacturing hardwood logs from harvested stems (log bucking) reduces the value of logs produced. Recent studies have estimated losses in the range from 28% to 38% in the lake states region. It has not, however, been clear how to correct the problem. Efforts to improve value recovery have...

Changing Tires En Route: Michigan Rolls out Millions in School Improvement Grants

ERIC Educational Resources Information Center

Scott, Caitlin

2011-01-01

A recent massive infusion of federal funding marked a dramatic shift in the federal approach to helping low-performing schools. As part of the broad array of economic stimulus efforts included in the American Recovery and Reinvestment Act of 2009 (ARRA), the U.S. Congress appropriated an extra $3 billion for school improvement grants (SIGs) to…

Analysis of health trait data from on-farm computer systems in the U.S. II: Comparison of genomic analyses including two-stage and single-step methods

USDA-ARS?s Scientific Manuscript database

The development of genomic selection methodology, with accompanying substantial gains in reliability for low-heritability traits, may dramatically improve the feasibility of genetic improvement of dairy cow health. Many methods for genomic analysis have now been developed, including the “Bayesian Al...

Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

PubMed

Roviello, Giandomenico; Zanotti, Laura; Cappelletti, Maria Rosa; Gobbi, Angela; Dester, Martina; Paganini, Giovanni; Pacifico, Chiara; Generali, Daniele; Roudi, Raheleh

2018-02-01

EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib changed dramatically the history of metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. However, not enough data are available on the efficacy of these targeted drugs in elderly patients. The aim of this study is to analyse the available clinical data evaluating the efficacy of anti-EGFR therapies in elderly patients with advanced NSCLC carrying EGFR mutations. A literature-based meta-analysis of the results of randomized clinical trials was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. Progression-free survival (PFS), as a measure of the efficacy of treatment, was the primary outcome investigated. The pooled analysis revealed an overall significant improvement in PFS (HR = 0.44, 95% CI 0.28-0.69; p = 0.0004) with the use of EGFR TKIs in EGFR-mutated NSCLC. The data stratification per age subgroups showed that EGFR TKIs were more effective in prolonging PFS in elderly patients, with HR 0.39 (p = 0.008), in comparison with young patients (HR = 0.48; p = 0.04). The results of this study suggest that EGFR TKIs have a significant effect in slowing down diseases progression in elderly patients with advanced NSCLC, therefore representing a valid therapeutic option in this age group.

Stigma Experienced by Children and Adolescents With Obesity.

PubMed

Pont, Stephen J; Puhl, Rebecca; Cook, Stephen R; Slusser, Wendelin

2017-12-01

The stigmatization of people with obesity is widespread and causes harm. Weight stigma is often propagated and tolerated in society because of beliefs that stigma and shame will motivate people to lose weight. However, rather than motivating positive change, this stigma contributes to behaviors such as binge eating, social isolation, avoidance of health care services, decreased physical activity, and increased weight gain, which worsen obesity and create additional barriers to healthy behavior change. Furthermore, experiences of weight stigma also dramatically impair quality of life, especially for youth. Health care professionals continue to seek effective strategies and resources to address the obesity epidemic; however, they also frequently exhibit weight bias and stigmatizing behaviors. This policy statement seeks to raise awareness regarding the prevalence and negative effects of weight stigma on pediatric patients and their families and provides 6 clinical practice and 4 advocacy recommendations regarding the role of pediatricians in addressing weight stigma. In summary, these recommendations include improving the clinical setting by modeling best practices for nonbiased behaviors and language; using empathetic and empowering counseling techniques, such as motivational interviewing, and addressing weight stigma and bullying in the clinic visit; advocating for inclusion of training and education about weight stigma in medical schools, residency programs, and continuing medical education programs; and empowering families to be advocates to address weight stigma in the home environment and school setting. Copyright © 2017 by the American Academy of Pediatrics.

SU-E-J-185: A Systematic Review of Breathing Guidance in Radiation Oncology and Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollock, S; Keall, P; Keall, R

Purpose: The advent of image-guided radiation therapy (IGRT) has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion is the use of breathing guidance systems during imaging and treatment. A review of such research had not yet been performed, it was therefore our aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. Methods: Results of online database searches were filtered in accordance tomore » a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with the PRISMAStatement reporting standard (Preferred Reporting Items for Systematic reviews and Meta-Analyses) utilizing the PICOS approach (Participants, Intervention, Comparison, Outcome, Study design). Participants: Cancer patients, healthy volunteers. Intervention: Biofeedback breathing guidance systems. Comparison: No breathing guidance of the same breathing type. Outcome: Regularity of breathing signal and anatomic/tumor motion, medical image quality, radiation treatment margins and coverage, medical imaging and radiation treatment times. Study design: Quantitative and controlled prospective or retrospective trials. Results: The systematic search yielded a total of 479 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. The vast majority of investigated outcomes were significantly positively impacted by the use of breathing guidance; however, this was dependent upon the nature of the breathing guidance system and study design. In 25/27 studies significant improvements from the use of breathing guidance were observed. Conclusion: The results found here indicate that further clinical studies are warranted which quantify more comprehensively the clinical impact of The results found here indicate that further clinical studies are warranted which quantify more comprehensively the clinical impact of breathing guidance interventions.« less

Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

NASA Astrophysics Data System (ADS)

Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

2008-02-01

Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

Status of vaccines for porcine epidemic diarrhea virus in the United States and Canada

USDA-ARS?s Scientific Manuscript database

In 2013, porcine epidemic diarrhea virus (PEDV) emerged in the United States as a rapidly spreading epidemic causing dramatic death losses in suckling piglets. Neonatal piglets are most vulnerable to clinical disease and their only protection is passive immunity from their dam. At the end of the thi...

Students as Resurrectionists--A Multimodal Humanities Project in Anatomy Putting Ethics and Professionalism in Historical Context

ERIC Educational Resources Information Center

Hammer, Rachel R.; Jones, Trahern W.; Hussain, Fareeda Taher Nazer; Bringe, Kariline; Harvey, Ronee E.; Person-Rennell, Nicole H.; Newman, James S.

2010-01-01

Because medical students have many different learning styles, the authors, medical students at Mayo Clinic, College of Medicine researched the history of anatomical specimen procurement, reviewing topic-related film, academic literature, and novels, to write, direct, and perform a dramatization based on Robert Louis Stevenson's "The…

A Review and Conceptual Framework for Integrating Leadership into Clinical Practice

ERIC Educational Resources Information Center

Kutz, Matthew R.

2012-01-01

Context: The purpose of this review is to assess leadership education and practice in athletic training. Leadership is a critical component of athletic training and health care. Leadership research in athletic training is dramatically behind other health care professions. Objective: To develop a model for integrating leadership behavior and…

Measurement of Attention and Related Functions in the Preschool Child

ERIC Educational Resources Information Center

Mahone, E. Mark

2005-01-01

The goal of this review of the clinical and research literature is to identify, describe, and critique published methods for assessment of attention and related functions in preschool children (ages 6 and younger). The need for valid assessment of preschool children has grown dramatically in the past two decades following the implementation of…

Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

ERIC Educational Resources Information Center

Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise.

PubMed

Saha, Supriya K; Zhu, Andrew X; Fuchs, Charles S; Brooks, Gabriel A

2016-05-01

Challenges in the diagnosis and classification of cholangiocarcinoma have made it difficult to quantify the true incidence of this highly aggressive malignancy. We analyzed the Surveillance, Epidemiology, and End Results data to assess long-term trends in the age-standardized incidence of intrahepatic and extrahepatic cholangiocarcinoma between 1973 and 2012, correcting for systematic coding errors. Because intrahepatic cholangiocarcinoma (ICC) may frequently be misdiagnosed as cancer of unknown primary (CUP), we also analyzed trends in the incidence of CUP. Between 1973 and 2012, the reported U.S. incidence of ICC increased from 0.44 to 1.18 cases per 100,000, representing an annual percentage change (APC) of 2.30%; this trend has accelerated during the past decade to an APC of 4.36%. The incidence of extrahepatic cholangiocarcinoma increased modestly from 0.95 to 1.02 per 100,000 during the 40-year period (APC, 0.14%). The incidence of CUP with histologic features potentially consistent with cholangiocarcinoma decreased by 51% between 1973 and 2012 (APC, -1.87%), whereas the incidence of CUP with squamous or nonepithelial histologic features increased modestly (APC, 0.42%). The recognized incidence of ICC in the U.S. continues to rise, whereas the incidence of ECC is stable. The incidence of CUP has fallen dramatically during the same time period. Clinical distinctions between cholangiocarcinoma (particularly intrahepatic cholangiocarcinoma [ICC]) and cancer of unknown primary (CUP) can be challenging. Recent discoveries have identified recurrent and potentially targetable genomic abnormalities in ICC, highlighting the importance of improving diagnosis. This study demonstrates that the incidence of ICC is increasing in the U.S., whereas the incidence of extrahepatic cholangiocarcinoma is stable. Concomitantly, the incidence of CUP has declined dramatically, suggesting that improved distinction between ICC and CUP may be a major driver of the increasing recognized incidence of ICC. The increasing incidence of ICC warrants further study of prevention and treatment approaches. ©AlphaMed Press.

Metabolic Syndrome Predicts Refractoriness to Intravenous Thrombolysis in Acute Ischemic Stroke.

PubMed

Dorado, Laura; Arenillas, Juan F; López-Cancio, Elena; Hernández-Pérez, María; Pérez de la Ossa, Natalia; Gomis, Meritxell; Millán, Mònica; Granada, María Luisa; Galán, Amparo; Palomeras, Ernest; Dávalos, Antoni

2015-11-01

Metabolic syndrome (MetS) has been associated with higher resistance to clot lysis at 24 hours after tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke. We aimed to test this hypothesis at earlier time points, when neurointerventional rescue procedures may still be indicated to achieve arterial recanalization. This is a prospective and observational study in consecutive stroke patients with MCA occlusion treated with IV tPA. MetS was diagnosed following the unified criteria of the last Joint Interim Statement 2009 participating several major organizations. The primary outcome variable was resistance to thrombolysis, defined as the absence of complete middle cerebral artery recanalization 2 hours after tPA bolus assessed by transcranial color-coded duplex or when rescue mechanical thrombectomy after IV tPA was required. Secondary outcome variables were dramatic neurological improvement (decrease in ≥10 points, or a National Institutes of Health Stroke Scale [NIHSS] score of 0-1 at 24 hours), symptomatic intracerebral hemorrhage following European-Australasian Acute Stroke Study II criteria, infarct volume at 24 hours (calculated by using the formula for irregular volumes, ABC/2), and good outcome (modified Rankin Scale score < 3) at 3 months. A total of 234 patients (median baseline NIHSS score 16 [10-20]) were included and 146 (62.4%) fulfilled MetS criteria. After multivariate analysis, MetS emerged as an independent predictor of resistance to thrombolysis (odds ratio = 2.2 [1.3-4.2], P = .01) and absence of dramatic neurological improvement (odds ratio = .5 [.28-.97], P = .04). In addition, MetS conferred poorer functional outcome, higher symptomatic intracerebral hemorrhage rate, and increased infarct volume, although these associations disappeared after adjustment for covariates. MetS predicts patients with middle cerebral artery occlusion refractory to early clot dissolution after IV tPA. This finding may help in acute clinical decision-making. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients

PubMed Central

2012-01-01

Objectives This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. Study design We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Results Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups. Conclusions In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients. PMID:23039212

Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients.

PubMed

Tong, Guo Qing; Cao, Shan Ren; Wu, Xun; Zhang, Jun Qiang; Cui, Ji; Heng, Boon Chin; Ling, Xiu Feng

2012-10-05

This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups. In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.

Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

PubMed

Smith, Tracy T; Rupprecht, Laura E; Denlinger-Apte, Rachel L; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C; Sved, Alan F

2017-09-01

A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction. This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of preclinical research for research questions related to nicotine reduction. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Real-time subway information for improving transit ridership.

DOT National Transportation Integrated Search

2016-08-01

In recent years, the standardization of transit schedule information has yielded a dramatic increase in the accessibility of computerized transit schedules and given rise to real-time service schedules. Two such real-time service schedules are the Ge...

Direct Formalin Fixation Induces Widespread Genomic Effects in Archival Tissues

EPA Science Inventory

Recent advances in next generation sequencing have dramatically improved transcriptional analysis of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. However, little is known about potential genomic artifacts induced by formalin fixation, which could affect toxi...

Zooming in on heat at Baghdad Sulcus

NASA Image and Video Library

2010-02-23

This map shows a dramatically improved view of heat radiation from a warm fissure near the south pole of Saturn icy moon Enceladus. It was obtained by NASA Cassini spacecraft during its Nov. 21, 2009, flyby of that moon.

Polyploidization without mitosis improves in vivo liver transduction with lentiviral vectors.

PubMed

Pichard, Virginie; Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas

2013-02-01

Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy.