Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD) is associated with postoperative cognitive decline. One of the proposed underlying mechanisms is the surgical procedure with the lead trajectory penetrating the caudate nucleus. Objective: To study whether penetration of the caudate nucleus affects neuropsychological outcome. Methods: Neuropsychological and imaging data of 30 PD patients who underwent bilateral STN DBS were analysed. Lead trajectories were evaluated leading to a group with (n = 10) and a group without penetration of the caudate nucleus (n = 20). The neuropsychological performance of each group was compared to baseline, both at 3 and 12 months postoperatively. Results: Only the Trail-Making Test part B (TMT-B) showed an interaction effect within the groups over time at 3 months postoperatively. At 12 months postoperatively, there was only a main effect of time with a decrease in performance in TMT-B for both groups. Also verbal fluency showed a significant decrease over time for both groups at 3 and 12 months postoperatively. Conclusion: Caudate nucleus penetration affects cognitive flexibility only in the short term after surgery.
Stereotact Funct Neurosurg 2016;94:413-420
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Πέμπτη 22 Δεκεμβρίου 2016
The impaired and/or disabled anesthesiologist.
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Splenic irradiation for splenomegaly: a systematic review
Publication date: Available online 22 December 2016
Source:Cancer Treatment Reviews
Author(s): Nicholas G. Zaorsky, Graeme R. Williams, Stefan K. Barta, Nestor F Esnaola, Patricia L. Kropf, Shelly B. Hayes, Joshua E. Meyer
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10 Gy in 1 Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12 months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r2 all < 0.4); therefore, lower doses (e.g. 5 Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
Graphical abstract
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Rituximab: 13 Open Questions after 20 Years of Clinical Use
Source:Cancer Treatment Reviews
Author(s): Francesca Pavanello, Emanuele Zucca, Michele Ghielmini
Rituximab improved the prognosis of all B-cell derived lymphoproliferative diseases, but despite 20 years of intensive use, it remains a drug with a number of still obscure characteristics and unanswered questions. These include the mechanism of action and of resistance, the optimal schedule, the interaction with chemotherapy, as well as predictive factors for response rate and duration. Despite being very well tolerated, the question of its long term side effects and the risks of the administration near to a pregnancy have only recently been addressed. Also the indications are still not all clear: rituximab induces remissions as a single agent and improves the effect of chemotherapy, but its use as maintenance or as a substitute for watch and wait is still debated. Also, it is still unclear if its efficacy derives at least partly by reducing the risk of histological transformation in indolent NHL and reducing the risk of CNS relapse in aggressive NHL. Finally, despite of 20 years of research, it is still unclear if rituximab can be efficiently substituted by biosimilars or new anti-CD20 antibodies. In this review we address all these questions and analyze the literature addressing these aspects.
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A comparison of two models of dental care for Aboriginal communities in New South Wales
Abstract
Background
Aboriginal people, and particularly those in rural areas, continue to suffer very high levels of dental disease despite significant reductions in the wider Australian population in the past 30 years. Until recently, there has been a shortage of oral health clinicians and the majority have provided care in major cities. The NSW Government funded various models of care for rural and regional areas and vulnerable population groups including Aboriginal people. This study utilises a comparative retrospective analysis to compare two models of oral health care for Aboriginal people including those living in rural NSW to inform future policy decisions.
Methods
Two models of public oral health care for Aboriginal patients in NSW were examined using publicly available descriptive information. Two years of funding and Dental Weighted Activity Units (DWAUs) data were analysed and regression analysis was used to compare the trends of monthly time series of DWAUs for the two different models.
Results
The cost per DWAU for Model A was significantly higher than Model B, and Model B delivered significantly more treatment over the period.
Conclusions
Based on the standardised national weighted pricing for public dentistry Model B offers significantly more services for less financial resources.
This article is protected by copyright. All rights reserved.
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Effectiveness of the European Chromium VI Directive for cement implementation on occupational allergic contact dermatitis occurrence: Assessment in France and UK
Hexavalent chromium is the main sensitizer in wet cement and a common cause of occupational allergic contact dermatitis (OACD), especially among workers in the construction industry.1,2 The European Chromium VI directive3 transposed into national regulations in France and UK respectively on May and January 2005, prohibits selling or using of hydrated cement with more than 0.0002% of chromium. This was achieved through the addition of ferrous sulphate to the dry product, allowing to reduce chromium VI to chromium III which is less sensitizing.
This article is protected by copyright. All rights reserved.
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Highly sensitive and low operating temperature SnO2 gas sensor doped by Cu and Zn two elements
Publication date: May 2017
Source:Sensors and Actuators B: Chemical, Volume 243
Author(s): Wenlong Zhang, Bin Yang, Jingquan Liu, Xiang Chen, Xiaolin Wang, Chunsheng Yang
In order to improve the sensitivity and reduce working temperature of tin oxide sensor, two elements of copper, zinc doped tin oxide gas sensor has been successfully synthesized using one-step hydrothermal method. During the preparation process, the common zinc acetate and cupric chloride were adopted as copper, zinc source, respectively. The morphology and structure of the as-prepared sample were further characterized using X-ray diffraction (XRD), energy dispersive spectrometry (EDS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HR-TEM), selected area electron diffraction (SAED), and ASAP 2460 (used for mesoporous distribution analysis). It's found that octahedral nanoparticle enclosed by (221) high energy crystal facet had been prepared. The results also demonstrated that the as-prepared tin oxide doped by copper, zinc elements was single crystal structure of tetragonal system and the size of the crystalline grain was about 50nm. During the gas sensing performance experiments, the sample's gas-sensing properties have been proved to be greatly enhanced in sensitivity and working temperature. The response value to 50ppm ethanol at 110°C of the sample was increased to 210 that was almost 10 times higher than reported values. Besides, the optimal working temperature was decreased to be 110°C from reported 350°C.
Graphical abstract
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Use of pyrolyzed paper as disposable substrates for voltammetric determination of trace metals
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Luiz André Juvêncio Silva, Weberson Pereira da Silva, Jason G. Giuliani, Sheila Cristina Canobre, Carlos D. Garcia, Rodrigo Alejandro Abarza Munoz, Eduardo Mathias Richter
The possibility of using pyrolyzed paper as disposable working electrodes for trace metals determination is reported for the first time. A small piece of pyrolyzed paper (0.7×0.7cm) was positioned at the bottom side of the electrochemical cell using a rubber O-ring, which defined the electrode area (0.48cm; 0.18cm2). A large number of electrodes can be obtained from a single piece of standard dimensions (2.5cm×7.5cm) of paper, therefore minimizing the cost per unit. The electrochemical performance of the pyrolyzed paper was demonstrated by cyclic voltammetry, electrochemical impedance spectroscopy and by the determination of Zn, Cd, and Pb by square-wave anodic stripping voltammetry. The unmodified pyrolyzed paper showed excellent performance for Pb and Cd detection (LOD =0.19 and 0.16 ppb, respectively). In the presence of Bi3+(in-situ film formation), the simultaneous determination of Zn, Cd and Pb was also possible (LOD=0.26, 0.25, and 0.39 ppb, respectively).
Graphical abstract
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Au Decorated ZnO hierarchical architectures: Facile synthesis, tunable morphology and enhanced CO detection at room temperature
Publication date: May 2017
Source:Sensors and Actuators B: Chemical, Volume 243
Author(s): S. Arunkumar, Tianfeng Hou, Young-Bae Kim, Byungchul Choi, Su Han Park, Seunghun Jung, Dong-Weon Lee
A highly selective and sensitive gas sensing material was prepared by decorating gold (Au) nanoparticles on zinc oxide (ZnO) nanostructure. First, zinc oxide architectures were synthesised through facile one-pot hydrothermal synthesis route by using zinc acetate as the metal precursors, ethanolamine as the organic Lewis base and water as the reaction medium. The versatile zinc oxide architectures such as (i) nanostars (ZNS), (ii) marigold flower (ZMF), (iii) nanorods assembled flower (ZNF) and (iv) nanorods (ZNR) were successfully synthesised by the controlled variation of the reaction medium mole ratio. The crystal structure and morphological evaluation of the as prepared material were investigated in detail by several analytical techniques, and the findings are consistent with each other. The carbon monoxide (CO) sensing ability of the as prepared materials was carried out at different sensing temperature (Ts≤300°C) and at different gas concentration (5–1000ppm). Gas sensing study clearly shows that the sensor responses are found to be morphology and surface area dependent. Among all the zinc oxide nanostructures, nanostars exhibits excellent sensitivity (SR∼31 toward 5ppm) at the optimized sensing temperature of 275°C. Further, to improve the sensing characteristics and to reduce the operating temperature, different wt% of gold nanopartilces were decorated on the surface of zinc oxide nano-stars by solution impregnation technique. Surface decoration of only 3wt% gold nanoparticles incorporated zinc oxide nanostars exhibits enhanced sensing response (SR ∼15 toward 50ppm) at 35°C with an excellent response (ΓRES ∼8s) and recovery (ΓREC ∼15s) time. Sensor also posses excellent selectivity toward CO compare to other interfering gases such as methanol, ethanol, acetone and hydrogen.
http://ift.tt/2hiIyZ7
Effectiveness of the European Chromium VI Directive for cement implementation on occupational allergic contact dermatitis occurrence: Assessment in France and UK
Hexavalent chromium is the main sensitizer in wet cement and a common cause of occupational allergic contact dermatitis (OACD), especially among workers in the construction industry.1,2 The European Chromium VI directive3 transposed into national regulations in France and UK respectively on May and January 2005, prohibits selling or using of hydrated cement with more than 0.0002% of chromium. This was achieved through the addition of ferrous sulphate to the dry product, allowing to reduce chromium VI to chromium III which is less sensitizing.
This article is protected by copyright. All rights reserved.
http://ift.tt/2imjlcj
Ultrasonic-promoted rapid TLP bonding of fine-grained 7034 high strength aluminum alloys
Publication date: May 2017
Source:Ultrasonics Sonochemistry, Volume 36
Author(s): Weibing Guo, Xuesong Leng, Tianmin Luan, Jiuchun Yan, Jingshan He
High strength aluminum alloys are extremely sensitive to the thermal cycle of welding. An ultrasonic-promoted rapid TLP bonding with an interlayer of pure Zn was developed to join fine-grained 7034 aluminum alloys at the temperature of lower 400°C. The oxide film could be successfully removed with the ultrasonic vibration, and the Al-Zn eutectic liquid phase generated once Al and Zn contacted with each other. Longer ultrasonic time can promote the diffusion of Zn into the base metal, which would shorten the holding time to complete isothermal solidification. The joints with the full solid solution of α-Al can be realized with the ultrasonic action time of 60s and holding time of only 3min at 400°C, and the shear strength of joints could reach 223MPa. The joint formation mechanism and effects of ultrasounds were discussed in details.
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Excitation energy transfer in ruthenium (II)-porphyrin conjugates led to enhanced emission quantum yield and 1O2 generation
Publication date: April 2017
Source:Journal of Luminescence, Volume 184
Author(s): Jie Pan, Lijun Jiang, Chi-Fai Chan, Tik-Hung Tsoi, Kwok-Keung Shiu, Daniel W.J. Kwong, Wing-Tak Wong, Wai-Kwok Wong, Ka-Leung Wong
Porphyrins are good photodynamic therapy (PDT) agents due to its flexibility for modifications to achieve tumor localization and photo-cytotoxicity against cancer. Yet they are not perfect. In a Ru(polypyridyl)-porphyrin system, the Ru(polypyridyl) moiety improves the water solubility and cell permeability. Consider the similar excited state energies between Ru(polypyridyl) and porphyrin moieties; a small perturbation (e.g. Zn(II) metalation) would lead to a marked change in the energy migration process. In this work, we have synthesized a series of porphyrins conjugated with Ru(polypyridyl) complexes using different linkers and investigated their photophysical properties, which included singlet oxygen quantum yield and their in vitro biological properties, resulting from linker variation and porphyrin modification by Zn(II) metalation.
Graphical abstract
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Fabrication of biodegradable Zn-Al-Mg alloy: Mechanical properties, corrosion behavior, cytotoxicity and antibacterial activities
Publication date: 1 April 2017
Source:Materials Science and Engineering: C, Volume 73
Author(s): H.R. Bakhsheshi-Rad, E. Hamzah, H.T. Low, M. Kasiri-Asgarani, S. Farahany, E. Akbari, M.H. Cho
In this work, binary Zn-0.5Al and ternary Zn-0.5Al-xMg alloys with various Mg contents were investigated as biodegradable materials for implant applications. Compared with Zn-0.5Al (single phase), Zn-0.5Al-xMg alloys consisted of the α-Zn and Mg2(Zn, Al)11 with a fine lamellar structure. The results also revealed that ternary Zn-Al-Mg alloys presented higher micro-hardness value, tensile strength and corrosion resistance compared to the binary Zn-Al alloy. In addition, the tensile strength and corrosion resistance increased with increasing the Mg content in ternary alloys. The immersion tests also indicated that the corrosion rates in the following order Zn-0.5Al-0.5Mg<Zn-0.5Al-0.3Mg<Zn-0.5Al-0.1Mg<Zn-0.5Al. The cytotoxicity tests exhibited that the Zn-0.5Al-0.5Mg alloy presents higher viability of MC3T3-E1 cell compared to the Zn-0.5Al alloy, which suggested good biocompatibility. The antibacterial activity result of both Zn-0.5Al and Zn-0.5Al-Mg alloys against Escherichia coli presented some antibacterial activity, while the Zn-0.5Al-0.5Mg significantly prohibited the growth of Escherichia coli. Thus, Zn-0.5Al-0.5Mg alloy with appropriate mechanical properties, low corrosion rate, good biocompatibility and antibacterial activities was believed to be a good candidate as a biodegradable implant material.
Graphical abstract
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Synthesis, spectroscopic, cyclic voltammetry properties and molecular structure of the thiocyanato-N meso-tetratolylporphyrinato zinc(II) ion complex
Publication date: 5 April 2017
Source:Journal of Molecular Structure, Volume 1133
Author(s): Zouhour Denden, Wafa Harhouri, Leila Ben Haj Hassen, Yoann Rousselin, Eric Saint-Aman, Habib Nasri
This paper describes the synthesis of the (thiocyanato-N)(meso-tetratolylporphyrinato)zinc(II) chlorobenzene monosolvate complex with the formula [K(2,2,2-crypt)][Zn(TTP)(NCS)]·C6H5Cl (I) using the cryptand-222 to solubilize potassium thiocyanate in chlorobenzene solvent. Complex (I) has been characterized by elementary analysis, IR, UV–vis, 1H NMR and MS, and the structure of this new zinc(II) metalloporphyrin been examined crystallographically. A cyclic voltammetry investigation was also carried out on this species. The title compound crystallizes in the triclinic, space group P-1, with a = 11.5151(7) Å, b = 15.212(10) Å, c = 20.1093(12) Å, α = 80.428(4)°, β = 74.926(4)°, γ = 84.704(4)°, V = 3364.7(4) Å3, Z = 2 and Dcal = 1.303 g cm−3. The porphyrin macrocycle of (I) exhibits moderate ruffling and saddle distortions. In the crystal, the [Zn(TTP)(NCS)]− ion complexes, the [K(2,2,2-crypt)]+ counterions and the chlorobenzene solvent molecules are involved in a number of weak C__H⋯S and C–H⋯π intermolecular interactions forming a three-dimensional framework.
Graphical abstract
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A rapid screening platform for catalyst discovery in azide–alkyne cycloaddition by ICP-MS/MS
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Qian He, Jia Wang, Yuxiang Mo, Chao Wei, Xiang Fang, Zhi Xing, Sichun Zhang, Xinrong Zhang
We developed a rapid high-throughput screening platform using a modified ICP-MS/MS system for monovalence metal ions catalysts discovery in azide–alkyne cycloaddition. Among the ten monovalence metal ions in the first row of periodic table containing Sc+, Ti+, V+, Cr+, Mn+, Fe+, Co+, Ni+, Cu+, and Zn+, five monovalence metal ions of Sc+, Co+, Ni+, Cu+ and Zn+ ions show relatively stronger catalytic activities than others. The catalytic mechanism of Sc+, Co+ and Ni+ ions is similar to the Cu+ ions, but Zn+ ions take a different catalytic route. A yields range of 77–98% for azide-alkyne cycloaddition was achieved with Sc+, Co+, Ni+, Cu+ and Zn+ ions as catalyst, respectively by using a UV laser ablation reactor in 20min, notable that the yields of Co+ and Sc+ ions were even higher than the common catalyst of Cu+ ions. The proposed platform would be used not only for catalyst discovery in azide-alkyne cycloaddition, but also for the discovery of single atom/ion catalysts in other organic reactions.
Graphical abstract
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Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations
Abstract
Background
Human rhinoviruses (HRVs) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells (MCs) play a key role in asthma where their numbers are increased in the bronchial epithelium with increasing disease severity.
Objective
In view of the emerging role of MCs in innate immunity and increased localisation to the asthmatic bronchial epithelium, we investigated whether HRV infection of MCs generated innate immune responses which were protective against infection.
Methods
The LAD2 MC line or primary human cord blood-derived MCs (CBMCs) were infected with HRV or UV-irradiated HRV at increasing multiplicities of infection (MOI) without or with IFN-β or IFN-λ. After 24 h, innate immune responses were assessed by RT-qPCR and IFN protein release by ELISA. Viral replication was determined by RT-qPCR and virion release by TCID50 assay.
Results
HRV infection of LAD2 MCs induced expression of IFN-β, IFN-λ and IFN-stimulated genes. However, LAD2 MCs were permissive for HRV replication and release of infectious HRV particles. Similar findings were observed with CBMCs. Neutralisation of the type I IFN receptor had minimal effects on viral shedding suggesting that endogenous type I IFN signalling offered limited protection against HRV. However, augmentation of these responses by exogenous IFN-β, but not IFN-λ, protected MCs against HRV infection.
Conclusion and clinical relevance
MCs are permissive for the replication and release of HRV which is prevented by exogenous IFN-β treatment. Taken together these findings suggest a novel mechanism whereby MCs may contribute to HRV-induced asthma exacerbations.
This article is protected by copyright. All rights reserved.
http://ift.tt/2i165x2
Selenite modulates the level of phenolics and nutrient element to alleviate the toxicity of arsenite in rice (Oryza sativa L.)
Publication date: April 2017
Source:Ecotoxicology and Environmental Safety, Volume 138
Author(s): Reshu Chauhan, Surabhi Awasthi, Preeti Tripathi, Seema Mishra, Sanjay Dwivedi, Abhishek Niranjan, Shekhar Mallick, Pratibha Tripathi, Veena Pande, Rudra Deo Tripathi
Arsenic (As) contamination of paddy rice is a serious threat all over the world particularly in South East Asia. Selenium (Se) plays important role in protection of plants against various abiotic stresses including heavy metals. Moreover, arsenite (AsIII) and selenite (SeIV) can be biologically antagonistic due to similar electronic configuration and sharing the common transporter for their uptake in plant. In the present study, the response of oxidative stress, phenolic compounds and nutrient elements was analyzed to investigate Se mediated As tolerance in rice seedlings during AsIII and SeIV exposure in hydroponics. Selenite (25µM) significantly decreased As accumulation in plant than As (25µM) alone treated plants. Level of oxidative stress related parameters viz., reactive oxygen species (ROS), lipid peroxidation, electrical conductivity, nitric oxide and pro-oxidant enzyme (NADPH oxidase), were in the order of As>As+Se>control>Se. Selenium ameliorated As phytotoxicity by increased level of phenolic compounds particularly gallic acid, protocatechuic acid, ferulic acid and rutin and thiol metabolism related enzymes viz., serine acetyl transferase (SAT) and cysteine synthase (CS). Selenium supplementation enhanced the uptake of nutrient elements viz., Fe, Mn, Co, Cu, Zn, Mo, and improved plant growth. The results concluded that Se addition in As contaminated environment might be an important strategy to reduce As uptake and associated phytotoxicity in rice plant by modulation of phenolic compounds and increased uptake of nutrient elements.
http://ift.tt/2hiM2ej
Performance of Mn-Zn ferrite magnetic fluid in a prototype distribution transformer under varying loading conditions
Publication date: April 2017
Source:International Journal of Thermal Sciences, Volume 114
Author(s): Jaykumar Patel, Kinnari Parekh, R.V. Upadhyay
The temperature distribution performance of prototype transformer has been evaluated for varying loads. A 3 KVA single phase transformer is prototyped for this purpose and thermocouples were inserted at various places for the study. A novel temperature sensitive magnetic fluid (TSMF - Mn-Zn ferrite magnetic fluid) is proposed to improve the cooling performance. Winding temperature reduces when prototype transformer is submerged in TSMF compared to the same experiment performed with transformer oil, for all loading (normal load, under load, overload). The reduction in temperature with TSMF attributes to the thermo-magnetic convection, and it is the maximum when the Curie temperature of the magnetic fluid is comparable to the hot spot temperature of the transformer. The experimental results match with numerical calculation and the existing simulation. The maximum cooling is observed with TSMF for overload condition and increases normal life expectancy nine times. In case of planned overload condition normal life expectancy doubles for all situations. Study leads to the conclusion that TSMF works as a better transformer coolant under all conditions, delivers more power than its nameplate rating without using any external accessories, and improves normal life of transformer. This will reduce the basic investment cost and maintenance of transformer.
Graphical abstract
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Using Objective Structured Clinical Examinations to Assess Intern Orthopaedic Physical Examination Skills: A Multimodal Didactic Comparison
Publication date: Available online 21 December 2016
Source:Journal of Surgical Education
Author(s): Donna Phillips, Christian A. Pean, Kathleen Allen, Joseph Zuckerman, Kenneth Egol
Patient care is 1 of the 6 core competencies defined by the Accreditation Council for Graduate Medical Education (ACGME). The physical examination (PE) is a fundamental skill to evaluate patients and make an accurate diagnosis. The purpose of this study was to investigate 3 different methods to teach PE skills and to assess the ability to do a complete PE in a simulated patient encounter.DesignProspective, uncontrolled, observational.SettingNortheastern academic medical center.ParticipantsA total of 32 orthopedic surgery residents participated and were divided into 3 didactic groups: Group 1 (n = 12) live interactive lectures, demonstration on standardized patients, and textbook reading; Group 2 (n = 11) video recordings of the lectures given to Group 1 and textbook reading alone; Group 3 (n = 9): 90-minute modules taught by residents to interns in near-peer format and textbook reading.ResultsThe overall score for objective structured clinical examinations from the combined groups was 66%. There was a trend toward more complete PEs in Group 1 taught via live lectures and demonstrations compared to Group 2 that relied on video recording. Near-peer taught residents from Group 3 significantly outperformed Group 2 residents overall (p = 0.02), and trended toward significantly outperforming Group 1 residents as well, with significantly higher scores in the ankle (p = 0.02) and shoulder (p = 0.02) PE cases.ConclusionsThis study found that orthopedic interns taught musculoskeletal PE skills by near-peers outperformed other groups overall. An overall score of 66% for the combined didactic groups suggests a baseline deficit in first-year resident musculoskeletal PE skills. The PE should continue to be taught and objectively assessed throughout residency to confirm that budding surgeons have mastered these fundamental skills before going into practice.
http://ift.tt/2i85zeb
New Media for Educating Urology Residents: An Interview Study in Canada and Germany
Publication date: Available online 22 December 2016
Source:Journal of Surgical Education
Author(s): Johannes Salem, Hendrik Borgmann, Andrew MacNeily, Katharina Boehm, Marianne Schmid, Christer Groeben, Martin Baunacke, Johannes Huber
ObjectiveTo investigate the usage and perceived usefulness of new media for educating urology residents in Canada and Germany.DesignWe designed an 11-item online survey to assess the use and perceived usefulness of new media for education. We performed a comparative analysis.SettingThe survey was distributed via e-mail to 143 Canadian and 721 German urology residents.ParticipantsThe survey included 58 urology residents from Canada and 170 from Germany.ResultsA total of 58 residents from Canada (41% response rate) and 170 from Germany (24% response rate) responded to this survey. Residents spent 45% of their education time on new media. The Internet was used by 91% (n = 208) of the residents for professional education purposes, with a median time of 270 minutes (interquartile range [IQR]: 114-540) per month. Apps were used by 54% (n = 118) of the residents, with a median time of 101 minutes (IQR: 45-293) per month. A total of 23% (n = 47) of the residents used social media (SoMe) for education, with a median time of 90 minutes (IQR: 53-80) per month. In all, 100% (n = 228) rated the Internet, 76% (n = 173) apps, and 43% (n = 97) SoMe as being useful for professional education purposes. A total of 90% (n = 205) watched medical videos for education, and 89% (n = 203) of these videos were on surgical procedures. Canadian urology residents used more new media sources for professional education than did the Germans (58% vs. 41%, p < 0.001). The time spent for education on new media was higher among Canadian residents for the Internet (p < 0.001), apps (p < 0.001), and SoMe (p = 0.033). Canadian residents reported more privacy concerns (p < 0.001).ConclusionsNew media play a dominant role in the education of urology residents. The primary source for personal education in urology is the Internet. Future studies and technological developments should investigate and improve new media tools to optimize education during residency.
http://ift.tt/2i85yH9
Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study.
Objective: Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance. Study Design: A single-arm, open-label investigational-device clinical trial. Setting: Two private-practice and one hospital-based ENT clinics. Patients: Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment. Intervention: Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens. Main Outcome Measures: The primary safety endpoint was a determination of "no change" (PTA4
http://ift.tt/2hOo8pX
http://ift.tt/2hOo8pX
Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations
Abstract
Background
Human rhinoviruses (HRVs) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells (MCs) play a key role in asthma where their numbers are increased in the bronchial epithelium with increasing disease severity.
Objective
In view of the emerging role of MCs in innate immunity and increased localisation to the asthmatic bronchial epithelium, we investigated whether HRV infection of MCs generated innate immune responses which were protective against infection.
Methods
The LAD2 MC line or primary human cord blood-derived MCs (CBMCs) were infected with HRV or UV-irradiated HRV at increasing multiplicities of infection (MOI) without or with IFN-β or IFN-λ. After 24 h, innate immune responses were assessed by RT-qPCR and IFN protein release by ELISA. Viral replication was determined by RT-qPCR and virion release by TCID50 assay.
Results
HRV infection of LAD2 MCs induced expression of IFN-β, IFN-λ and IFN-stimulated genes. However, LAD2 MCs were permissive for HRV replication and release of infectious HRV particles. Similar findings were observed with CBMCs. Neutralisation of the type I IFN receptor had minimal effects on viral shedding suggesting that endogenous type I IFN signalling offered limited protection against HRV. However, augmentation of these responses by exogenous IFN-β, but not IFN-λ, protected MCs against HRV infection.
Conclusion and clinical relevance
MCs are permissive for the replication and release of HRV which is prevented by exogenous IFN-β treatment. Taken together these findings suggest a novel mechanism whereby MCs may contribute to HRV-induced asthma exacerbations.
This article is protected by copyright. All rights reserved.
http://ift.tt/2i165x2
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Arterial ligation versus embolization in epistaxis management: Counterintuitive national trends
Objectives/Hypothesis
Arterial ligation and embolization are treatment modalities indicated in severe and refractory epistaxis. The purpose of this study was to examine temporal trends and compare outcomes in treatment of hospitalized epistaxis patients with ligation or embolization.
Methods
This retrospective cohort analysis utilized the 2008 to 2013 National Inpatient Sample to identify patients admitted with a primary diagnosis of epistaxis, and an associated procedure code for ligation or embolization.
Results
A total of 1,813 cases met the inclusion criteria, with 57.1% undergoing ligation. During the study period, treatment with ligation has trended downward, whereas treatment with embolization has remained constant. Overall, ligated patients were older (64.1 vs. 62.4 years; P = 0.027) and had higher rates of congestive heart failure (15.1% vs. 9.8%; P = 0.001). No significant differences in rates of chronic pulmonary disease, coagulopathy, liver disease, or hereditary hemorrhagic telangiectasia were observed between cohorts. No differences were observed in rates of blood transfusion, stroke, blindness, or in-hospital mortality; however, ligated patients had lower rates of intubation/tracheostomy (2.8% vs. 5.3%; P = 0.009). Ligated patients also experienced shorter hospital stays (3.6 vs. 4.0 days; P = 0.014) and incurred lower hospital charges ($33,029 vs. $69,304; P < 0.001).
Conclusion
Compared to embolization, ligation is associated with significantly decreased hospital charges and shorter hospital stay, without an increase in complication rates. Counterintuitively, ligation appears to be trending downward nationally in its use relative to embolization.
Level of Evidence
2C. Laryngoscope, 2016
http://ift.tt/2hYUrAk
Voice disorders and associated risk markers among young adults in the United States
Objectives/Hypothesis
To examine the prevalence of voice disorders in young adults and identify sociodemographic factors, health conditions, and behaviors associated with voice disorder prevalence.
Study Design
Cross-sectional analysis of data from the National Longitudinal Study of Adolescent to Adult Health.
Methods
During home interviews, 14,794 young adults, aged 24 to 34 years, reported their health conditions and behaviors. Presence and duration of voice disorders were reported over the past 12 months. We computed overall and stratified prevalence estimates by age, gender, race/ethnicity, medical conditions, smoking, and alcohol use. Multiple logistic regression was used to identify independent risk factors for a voice disorder while accounting for the complex sample design.
Results
Six percent of participants reported a voice disorder lasting at least 3 days. Females had 56% greater odds of voice disorders than males. Number of days drinking alcohol was associated with voice disorders, but number of smoking days was not. Conditions that increased the likelihood of voice disorders included hypertension (OR = 1.42 [95% confidence interval {CI}: 1.07-1.89]), tinnitus (OR = 1.53 [95% CI: 1.06-2.20]), and anxiety/panic disorder (OR = 1.26 [95% CI: 1.00-1.60]). Results were independent of gender, alcohol consumption, upper respiratory symptoms, and lower respiratory conditions including asthma, bronchitis/emphysema, and gastrointestinal symptoms (diarrhea/nausea/vomiting).
Conclusions
Voice disorders in young adulthood were associated with hypertension, tinnitus, and anxiety. Greater awareness of these relationships may facilitate voice evaluation among people who seek healthcare for these chronic conditions.
Level of Evidence
2b Laryngoscope, 2016
http://ift.tt/2hfi6hd
Lower airway disease and pituitary surgery: Is there an association with postoperative cerebrospinal fluid leak?
Objectives/Hypothesis
To explore the relationship between lower airway disease and postoperative cerebrospinal fluid (CSF) rhinorrhea among patients undergoing pituitary surgery
Study Design
Retrospective review.
Methods
A retrospective review of the Healthcare Cost and Utilization Project's 2013 National Inpatient Sample was conducted to characterize the hospital stay and surgical outcomes of patients undergoing pituitary surgery. Patients with lower airway disease (including chronic obstructive pulmonary disease and asthma) were compared to a disease-free population identifying demographics and complications over-represented in the lower airway group.
Results
The majority of hypophysectomies (92.1%) were performed via a transsphenoidal approach. Among transsphenoidal patients, individuals with asthma (92.8% of the lower airway disease cohort) harbored a greater postoperative CSF leak rate (4.7% vs. 2.7%, P = .022), and were more likely to develop postoperative diabetes insipidus (6.2% vs. 4.1%, P = .024) and neurological complications (13.0% vs. 9.6%, P = .010) when compared to a lower airway disease-free cohort. Patients with CSF rhinorrhea had longer lengths of stay (7.8 days vs. 4.5 days, P < .001) and higher discharge costs ($148,309 vs. $76,246, P < .001). A binary logistic regression model identified having asthma (P = .042), being female (P = .011), and having gastroesophageal reflux disease (P = .006) as independent predictors of postoperative CSF rhinorrhea.
Conclusions
Several patient comorbidities including asthma are associated with a greater risk of postoperative CSF rhinorrhea. Perioperative lower airway assessment and disease control may potentially decrease one's risk of this complication, although further inquiry is urgently needed to identify optimal preventive strategies.
Level of Evidence
2c. Laryngoscope, 2016
http://ift.tt/2hYIlHF
Arterial ligation versus embolization in epistaxis management: Counterintuitive national trends
Objectives/Hypothesis
Arterial ligation and embolization are treatment modalities indicated in severe and refractory epistaxis. The purpose of this study was to examine temporal trends and compare outcomes in treatment of hospitalized epistaxis patients with ligation or embolization.
Methods
This retrospective cohort analysis utilized the 2008 to 2013 National Inpatient Sample to identify patients admitted with a primary diagnosis of epistaxis, and an associated procedure code for ligation or embolization.
Results
A total of 1,813 cases met the inclusion criteria, with 57.1% undergoing ligation. During the study period, treatment with ligation has trended downward, whereas treatment with embolization has remained constant. Overall, ligated patients were older (64.1 vs. 62.4 years; P = 0.027) and had higher rates of congestive heart failure (15.1% vs. 9.8%; P = 0.001). No significant differences in rates of chronic pulmonary disease, coagulopathy, liver disease, or hereditary hemorrhagic telangiectasia were observed between cohorts. No differences were observed in rates of blood transfusion, stroke, blindness, or in-hospital mortality; however, ligated patients had lower rates of intubation/tracheostomy (2.8% vs. 5.3%; P = 0.009). Ligated patients also experienced shorter hospital stays (3.6 vs. 4.0 days; P = 0.014) and incurred lower hospital charges ($33,029 vs. $69,304; P < 0.001).
Conclusion
Compared to embolization, ligation is associated with significantly decreased hospital charges and shorter hospital stay, without an increase in complication rates. Counterintuitively, ligation appears to be trending downward nationally in its use relative to embolization.
Level of Evidence
2C. Laryngoscope, 2016
http://ift.tt/2hYUrAk
Voice disorders and associated risk markers among young adults in the United States
Objectives/Hypothesis
To examine the prevalence of voice disorders in young adults and identify sociodemographic factors, health conditions, and behaviors associated with voice disorder prevalence.
Study Design
Cross-sectional analysis of data from the National Longitudinal Study of Adolescent to Adult Health.
Methods
During home interviews, 14,794 young adults, aged 24 to 34 years, reported their health conditions and behaviors. Presence and duration of voice disorders were reported over the past 12 months. We computed overall and stratified prevalence estimates by age, gender, race/ethnicity, medical conditions, smoking, and alcohol use. Multiple logistic regression was used to identify independent risk factors for a voice disorder while accounting for the complex sample design.
Results
Six percent of participants reported a voice disorder lasting at least 3 days. Females had 56% greater odds of voice disorders than males. Number of days drinking alcohol was associated with voice disorders, but number of smoking days was not. Conditions that increased the likelihood of voice disorders included hypertension (OR = 1.42 [95% confidence interval {CI}: 1.07-1.89]), tinnitus (OR = 1.53 [95% CI: 1.06-2.20]), and anxiety/panic disorder (OR = 1.26 [95% CI: 1.00-1.60]). Results were independent of gender, alcohol consumption, upper respiratory symptoms, and lower respiratory conditions including asthma, bronchitis/emphysema, and gastrointestinal symptoms (diarrhea/nausea/vomiting).
Conclusions
Voice disorders in young adulthood were associated with hypertension, tinnitus, and anxiety. Greater awareness of these relationships may facilitate voice evaluation among people who seek healthcare for these chronic conditions.
Level of Evidence
2b Laryngoscope, 2016
http://ift.tt/2hfi6hd
Lower airway disease and pituitary surgery: Is there an association with postoperative cerebrospinal fluid leak?
Objectives/Hypothesis
To explore the relationship between lower airway disease and postoperative cerebrospinal fluid (CSF) rhinorrhea among patients undergoing pituitary surgery
Study Design
Retrospective review.
Methods
A retrospective review of the Healthcare Cost and Utilization Project's 2013 National Inpatient Sample was conducted to characterize the hospital stay and surgical outcomes of patients undergoing pituitary surgery. Patients with lower airway disease (including chronic obstructive pulmonary disease and asthma) were compared to a disease-free population identifying demographics and complications over-represented in the lower airway group.
Results
The majority of hypophysectomies (92.1%) were performed via a transsphenoidal approach. Among transsphenoidal patients, individuals with asthma (92.8% of the lower airway disease cohort) harbored a greater postoperative CSF leak rate (4.7% vs. 2.7%, P = .022), and were more likely to develop postoperative diabetes insipidus (6.2% vs. 4.1%, P = .024) and neurological complications (13.0% vs. 9.6%, P = .010) when compared to a lower airway disease-free cohort. Patients with CSF rhinorrhea had longer lengths of stay (7.8 days vs. 4.5 days, P < .001) and higher discharge costs ($148,309 vs. $76,246, P < .001). A binary logistic regression model identified having asthma (P = .042), being female (P = .011), and having gastroesophageal reflux disease (P = .006) as independent predictors of postoperative CSF rhinorrhea.
Conclusions
Several patient comorbidities including asthma are associated with a greater risk of postoperative CSF rhinorrhea. Perioperative lower airway assessment and disease control may potentially decrease one's risk of this complication, although further inquiry is urgently needed to identify optimal preventive strategies.
Level of Evidence
2c. Laryngoscope, 2016
http://ift.tt/2hYIlHF
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Decline in acute urinary toxicities with increased institutional experience: 15-year experience of permanent seed prostate brachytherapy in a single Australasian institution
Source:Brachytherapy
Author(s): Wee Loon Ong, Bronwyn Matheson, Jeremy Millar
PurposeTo evaluate the incidence of acute urinary toxicity after permanent seed prostate brachytherapy (BT) over a 15-year period.Methods and MaterialsThe study consisted of 782 prostate cancer patients treated with BT. All patients completed self-administered International Prostate Symptoms Score (IPSS) at baseline and during regular follow-up. We evaluated the risk of acute urinary retention (AUR) up to 3 months post-BT and lower urinary tract symptom (LUTS) resolution (defined as return to within two points of baseline IPSS score) at regular intervals, up to 24 months post-BT. Univariate and multivariate logistic regressions were used to evaluate the effect of various patient, tumor, and treatment factors on the risk of AUR and the likelihood of LUTS resolution.ResultsNinety-six patients (12%) developed AUR at a median of 1 day post-BT. Increased peak urinary flow is independently associated with lower risk of AUR (odds ratio [OR] = 0.94; 95% confidence interval [CI] = 0.91–0.97). Decline in incidence of AUR was observed over time with increased institutional experience (p = 0.03). Of the 646 patients with a minimum of 24-month follow-up, 29%, 49%, and 72% had LUTS resolution at 6, 12, and 24 months, respectively. Patients who had pre-BT transurethral resection of prostate (OR = 2.4; 95% CI = 1.5–4.0), cytoreductive neo-adjuvant androgen deprivation (OR = 2.0; 95% CI = 1.0–4.0), and higher baseline IPSS (OR = 1.1; 95% CI = 1.07–1.19) are more likely to report LUTS resolution at 24 months.ConclusionsWe reported decline in AUR over time with increased institutional experience in one of the largest Australasian BT series. Approximately three-quarters of patients achieved LUTS resolution at 24-month follow-up.
http://ift.tt/2iinYrP
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
A process-based emission model of volatile organic compounds from silage sources on farms
Source:Atmospheric Environment, Volume 152
Author(s): H.F. Bonifacio, C.A. Rotz, S.D. Hafner, F. Montes, M. Cohen, F.M. Mitloehner
Silage on dairy farms can emit large amounts of volatile organic compounds (VOCs), a precursor in the formation of tropospheric ozone. Because of the challenges associated with direct measurements, process-based modeling is another approach for estimating emissions of air pollutants from sources such as those from dairy farms. A process-based model for predicting VOC emissions from silage was developed and incorporated into the Integrated Farm System Model (IFSM, v. 4.3), a whole-farm simulation of crop, dairy, and beef production systems. The performance of the IFSM silage VOC emission model was evaluated using ethanol and methanol emissions measured from conventional silage piles (CSP), silage bags (SB), total mixed rations (TMR), and loose corn silage (LCS) at a commercial dairy farm in central California. With transport coefficients for ethanol refined using experimental data from our previous studies, the model performed well in simulating ethanol emission from CSP, TMR, and LCS; its lower performance for SB could be attributed to possible changes in face conditions of SB after silage removal that are not represented in the current model. For methanol emission, lack of experimental data for refinement likely caused the underprediction for CSP and SB whereas the overprediction observed for TMR can be explained as uncertainty in measurements. Despite these limitations, the model is a valuable tool for comparing silage management options and evaluating their relative effects on the overall performance, economics, and environmental impacts of farm production. As a component of IFSM, the silage VOC emission model was used to simulate a representative dairy farm in central California. The simulation showed most silage VOC emissions were from feed lying in feed lanes and not from the exposed face of silage storages. This suggests that mitigation efforts, particularly in areas prone to ozone non-attainment status, should focus on reducing emissions during feeding. For the simulated dairy farm, a reduction of around 30% was found if cows were housed and fed in a barn rather than in an open lot, and 23% if feeds were delivered as four feedings per day rather than as one. Reducing the exposed face of storage can also be useful. Simulated use of silage bags resulted in 90% and 18% reductions in emissions from the storage face and whole farm, respectively.
http://ift.tt/2h86FVe
Inhalation exposure and health risk levels to BTEX and carbonyl compounds of traffic policeman working in the inner city of Bangkok, Thailand
Source:Atmospheric Environment, Volume 152
Author(s): Navaporn Kanjanasiranont, Tassanee Prueksasit, Daisy Morknoy
Benzene, toluene, ethylbenzene and xylenes (BTEX) and carbonyl compounds (CCs) are recognized traffic-related air pollutants in urban environments and are the focus of this study. In Bangkok, the BTEX and CC concentrations in both ambient air and personal exposure samples were studied during two periods (April–May and August–September 2014) at four different sampling sites around the Pathumwan District (three intersections and one T-junction). Traffic policemen, representing the high-exposure group for these toxic air pollutants, were observed, and the health risk to these workers was evaluated. Toluene was the predominant aromatic compound in the ambient and personal exposure samples. The maximum average ambient concentration of BTEX was 2968.96 μg/m3. Formaldehyde and acetaldehyde were the most abundant CCs at all of the sampling sites, with the greatest mean concentrations of these substances being 21.50 μg/m3 and 64.82 μg/m3, respectively. In the personal exposure samples, the highest levels of BTEX, formaldehyde and acetaldehyde concentrations were 2231.85 μg/m3, 10.61 μg/m3, and 16.03 μg/m3, respectively. In terms of risk assessment, benzene posed the greatest cancer risk (at the 95% CI), followed by toluene, acetaldehyde and formaldehyde (1.15E-02, 5.14E-03, 2.84E-04, and 2.52E-04, respectively). Three risk factors were investigated to reduce the total cancer risk levels: reducing the chemical concentration, exposure time and exposure duration. The use of a mask (chemical concentration) was the best way to reduce the risk to traffic police. However, the risk value of benzene (average 1.57E-05) was still higher than an acceptable value when using a mask.
http://ift.tt/2i7Gfop
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations
Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. Results: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. Conclusions: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.
http://ift.tt/2hO67YV
Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis
Background: Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. Results: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Conclusions: Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).
http://ift.tt/2ii46VM
Use of Different Vegetable Products to Increase Preschool-Aged Children’s Preference for and Intake of a Target Vegetable: A Randomized Controlled Trial
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Victoire W.T. de Wild, Cees de Graaf, Gerry Jager
BackgroundChildren's low vegetable consumption requires effective strategies to enhance preference for and intake of vegetables.ObjectiveThe study compared three preparation practices for a target vegetable (spinach) on their effectiveness in increasing preschool-aged children's preference for and intake of the target vegetable in comparison to a control vegetable (green beans).DesignWe conducted a randomized controlled trial with four parallel groups: plain spinach, creamed spinach, spinach ravioli, and green beans. During the intervention, children were served the vegetable at their main meal six times over 6 weeks at home.Participants/settingChildren aged 2 to 4 years were recruited from six child-care centers located in Wageningen, the Netherlands, and randomly assigned to one of the four groups, with vegetable products provided by the researchers. The study was performed between September 2014 and January 2015. In total, 103 children participated, with 26, 25, 26, and 26 in the plain spinach, creamed spinach, spinach ravioli, and green beans groups, respectively.Main outcome measuresPreference for and ad libitum intake of cooked spinach were assessed during a test meal at the day-care center pre- and postintervention. Food neophobia was assessed via the Child Food Neophobia Scale.Statistical analyses performedGeneral linear model repeated measures analysis, including food neophobia, spinach liking, exposure, and consumption scores as covariates, was performed to test for effects of group on intake. Logistic regression was used to assess changes in preference between pre- and postintervention.ResultsAll four groups significantly increased their spinach intake from pre- (53 g) to postintervention (91 g) by an average of 70%. For preference, no significant shift toward the target vegetable was found from pre- to postintervention. The effect on intake depended on the child's neophobia status and preintervention spinach consumption, with children with neophobia being less responsive to the intervention and with children who ate more spinach before the intervention being more responsive to the intervention.ConclusionsThese findings suggest that repeated exposure to differently prepared spinach products, or even another green vegetable, improved children's spinach intake. However, children with neophobia may need a different approach.
http://ift.tt/2i7EOGx
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