Objective: New, value-based regulations and reimbursement structures are creating historic care management challenges, thinning the margins and threatening the viability of hospitals and health systems. The Society of Critical Care Medicine convened a taskforce of Academic Leaders in Critical Care Medicine on February 22, 2016, during the 45th Critical Care Congress to develop a toolkit drawing on the experience of successful leaders of critical care organizations in North America for advancing critical care organizations (Appendix 1). The goal of this article was to provide a roadmap and call attention to key factors that adult critical care medicine leadership in both academic and nonacademic setting should consider when planning for value-based care. Design: Relevant medical literature was accessed through a literature search. Material published by federal health agencies and other specialty organizations was also reviewed. Collaboratively and iteratively, taskforce members corresponded by electronic mail and held monthly conference calls to finalize this report. Setting: The business and value/performance critical care organization building section comprised of leaders of critical care organizations with expertise in critical care administration, healthcare management, and clinical practice. Measurements and Main Results: Two phases of critical care organizations care integration are described: "horizontal," within the system and regionalization of care as an initial phase, and "vertical," with a post-ICU and postacute care continuum as a succeeding phase. The tools required for the clinical and financial transformation are provided, including the essential prerequisites of forming a critical care organization; the manner in which a critical care organization can help manage transformational domains is considered. Lastly, how to achieve organizational health system support for critical care organization implementation is discussed. Conclusions: A critical care organization that incorporates functional clinical horizontal and vertical integration for ICU patients and survivors, aligns strategy and operations with those of the parent health system, and encompasses knowledge on finance and risk will be better positioned to succeed in the value-based world. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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Παρασκευή 1 Σεπτεμβρίου 2017
Cell-Free Plasma Hemoglobin and Male Gender Are Risk Factors for Acute Kidney Injury in Low Risk Children Undergoing Cardiopulmonary Bypass.
Objectives: To determine the relationship between the production of cell-free plasma hemoglobin and acute kidney injury in infants and children undergoing cardiopulmonary bypass for cardiac surgery. Design: Prospective observational study. Setting: Twelve-bed cardiac ICU in a university-affiliated children's hospital. Patients: Children were prospectively enrolled during their preoperative outpatient appointment with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass, no preexisting renal dysfunction. Interventions: None. Measurements and Main Results: Plasma and urine were collected at baseline (in a subset), the beginning and end of cardiopulmonary bypass, and 2 hours and 24 hours after cardiopulmonary bypass in 60 subjects. Levels of plasma hemoglobin increased during cardiopulmonary bypass and were associated (p 2 yr [R2 = 0.22; p
http://ift.tt/2wrTNEC
http://ift.tt/2wrTNEC
Sedation and Mobilization during Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Failure: An International Survey.
Objectives: To characterize sedation, analgesia, delirium, and mobilization practices in patients supported with venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. Design: Cross-sectional electronic survey administered January 2016 to March 2016. Setting: Three-hundred ninety-four extracorporeal membrane oxygenation centers registered with the Extracorporeal Life Support Organization. Subjects: Extracorporeal membrane oxygenation medical directors and program coordinators. Interventions: None. Measurements and Main Results: We analyzed responses from 209 respondents (53%), mostly from academic centers (63%); 41% respondents provide venovenous extracorporeal membrane oxygenation to adults exclusively. Following venovenous extracorporeal membrane oxygenation initiation, 97% respondents administer sedative/analgesic infusions, and the sedation target was "sedated" or "very sedated" for 59%, "calm and cooperative" for 25%, and "unarousable" for 16%. Use of daily sedation interruption and a sedation/analgesia protocol was reported by 51% and 39%, respectively. Midazolam (48%) and propofol (19%) were reported as the most frequently used sedatives; fentanyl (44%) and morphine (20%) the most frequent opioids. Use of a delirium scale was reported by 55% respondents. Physical therapy was reported by 84% respondents, with 41% initiating it within 72 hours after cannulation. Mobilization goals varied from range of motion exercises (81%) to ambulation (22%). The most frequently perceived barriers to mobilization were hemodynamic instability, hypoxemia, and dependency on venovenous extracorporeal membrane oxygenation support. Conclusions: The majority of respondents reported targeting moderate to deep sedation following cannulation, with the use of sedative and opioid infusions. There is considerable variability surrounding early physical therapy and mobilization goals for patients with acute respiratory failure supported by venovenous extracorporeal membrane oxygenation. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
http://ift.tt/2vSwDDI
http://ift.tt/2vSwDDI
Folic acid supplement use and the risk of gestational hypertension and preeclampsia
Publication date: Available online 1 September 2017
Source:Women and Birth
Author(s): Maria P.G. De Ocampo, Maria Rosario G. Araneta, Caroline A. Macera, John E. Alcaraz, Thomas R. Moore, Christina D. Chambers
BackgroundHypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality. Studies suggest that the use of folic acid may lower the risk of hypertensive disorders in pregnant women.AimThe aim of this study was to assess the effects of timing and duration of folic acid-containing supplement use on the risk for gestational hypertension and preeclampsia.MethodsExposures and outcomes data were obtained through interviews and review of participant's medical records from the MotherToBaby cohort studies across the United States and Canada. Demographics, medical history, lifestyle factors, substance use, and fetal sex were assessed as potential confounders. Unadjusted and adjusted risks for gestational hypertension and preeclampsia were examined using odds ratios and 95% confidence intervals.Findings3247 women were included in the study. Compared to non-supplement use, early and late supplement use were not significantly associated with the development of gestational hypertension or preeclampsia. The odds of developing gestational hypertension and preeclampsia were significantly reduced as the duration of folic acid-containing supplement use increased.ConclusionFindings from this study suggest that the use of folic acid-containing supplements may mitigate the risk for gestational hypertension and preeclampsia.
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Ascorbate Depletion Reduces TET2 Activity to Accelerate Leukemogenesis [Research Watch]
Elevated ascorbate levels maintain TET2 activity in HSCs and decline with differentiation.
http://ift.tt/2gyrxug
Local Delivery of IFN{alpha} Has Antitumor Activity in Bladder Cancer [Research Watch]
Intravesical delivery of rAd-IFNα/Syn3 is safe and achieves durable responses in high-grade NMIBC.
http://ift.tt/2eNg5HF
Distinct Tumor-Immune Microenvironments Occur at Different Tumor Sites [Research Watch]
Tumor regression was linked to immune infiltration in a patient with chemotherapy-treated ovarian cancer.
http://ift.tt/2gz3DyR
EWS-FLI1 Retargets BAF Chromatin Remodeling Complexes in Ewing Sarcoma [Research Watch]
BAF recruitment to GGAA microsatellites activates the Ewing sarcoma transcriptional program.
http://ift.tt/2eNeAcr
VEGFR Inhibitor-Resistant Thyroid Cancer Responds to Cabozantinib [Research Watch]
Cabozantinib achieved partial responses in 40% of patients with differentiated thyroid cancer (DTC).
http://ift.tt/2gxVhaB
CDK4/6 Inhibitors Induce Antitumor Immunity [News in Brief]
Cell cycle–blocking drugs enhance tumor antigen presentation and suppress regulatory T cells.
http://ift.tt/2eNzSXz
Recurrent tumor cell-intrinsic and -extrinsic alterations during MAPKi-induced melanoma regression and early adaptation [Research Articles]
Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively). Tumor cell-intrinsic reprogramming attenuated MAPK-dependency, while enhancing mesenchymal, angiogenic and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations.
http://ift.tt/2gytFCq
Variability in Interpretation of Cardiac Standstill Among Physician Sonographers
Cardiac standstill on point-of-care ultrasonography has been widely studied as a marker of prognosis in cardiac arrest. Return of spontaneous circulation has been reported in as few as 0% and as many as 45% of patients with cardiac standstill. When explicitly documented, the definition of cardiac activity in these studies varied from any slight change in echogenicity of the myocardium to any kinetic cardiac activity. We hypothesize that the variability in research definitions of cardiac activity may affect interpretation of video clips of patients in cardiac arrest.
http://ift.tt/2gwOj62
Associations of Body Mass Index and Body Fat With Markers of Inflammation and Nutrition Among Patients Receiving Hemodialysis
Understanding the extent to which visceral and subcutaneous body fat are associated with markers of nutrition and inflammation in patients on dialysis therapy could shed light on the obesity paradox and the biology of subcutaneous fat.
http://ift.tt/2vzcozy
Unexpired Lots of Oxytocin Compounded with Either Lactated Ringers or Lactated Ringers and Dextrose by PharMEDium - Recall - Sub-Potency
Audience: Pharmacy, Risk Manager Posted 09/01/2017] ISSUE: PharMEDium Services, LLC (PharMEDium) is voluntarily recalling all unexpired lots of Oxytocin compounded with Lactated Ringers and all unexpired lots of Oxytocin compounded with Lactated...
http://ift.tt/2eMQIWs
Alcohol Pads or Benzalkonium Chloride Antiseptic Towelettes by Foshan Flying Medical Products: FDA Alert - Lack of Sterility Assurance and Other Quality Issues
Audience: Pharmacy, Health Professional, Patient [Posted 09/01/2017] ISSUE: The U.S. Food and Drug Administration is alerting health care professionals and patients not to use alcohol pads or benzalkonium chloride antiseptic towelettes made by...
http://ift.tt/2gxKNZ5
Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection
& Aims: Hepatocellular (HCC) surveillance guidelines for patients with chronic hepatitis B virus (HBV) infection are based on race- and age-specific estimates of HCC risk, derived from studies conducted in areas in which HBV is endemic.
http://ift.tt/2erdwdF
Development and validation of a new scoring system to determine the necessity of small-bowel endoscopy in obscure gastrointestinal bleeding
Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established.
http://ift.tt/2eMRoLf
Cranial Electrotherapy Stimulation for the Management of Depression, Anxiety, Sleep Disturbance, and Pain in Patients with Advanced Cancer: A preliminary study
Cranial Electrotherapy Stimulation (CES) is a safe modulation of brain activity for treating depression, anxiety, insomnia, and pain. However, there are no published studies in patients with advanced cancer (ACP).
http://ift.tt/2gwPy50
Cancer pain with a neuropathic component: a cross-sectional study of its clinical characteristics, associated psychological distress, treatments and predictors at referral to a cancer pain clinic
In patients with cancer pain, identifying a neuropathic pain component (NPC) may inform the selection of subsequent therapeutic interventions.
http://ift.tt/2eNs1Jn
Identification of ATIC as a novel target for chemoradiosensitization
Detection of a frameshift mutation in the gene encoding the purine biosynthetic enzyme ATIC in a panel of radiosensitive individuals prompted studies to elucidate the role of ATIC in DNA damage responses and ascertain whether inhibition of ATIC might be an effective chemoradiosensitization strategy. Knockdown of ATIC or inhibition of its enzymatic activity compromised DNA double strand break repair and reduced cell survival after irradiation.
http://ift.tt/2wYxOXr
Unexpired Lots of Oxytocin Compounded with Either Lactated Ringers or Lactated Ringers and Dextrose by PharMEDium - Recall - Sub-Potency
Audience: Pharmacy, Risk Manager Posted 09/01/2017] ISSUE: PharMEDium Services, LLC (PharMEDium) is voluntarily recalling all unexpired lots of Oxytocin compounded with Lactated Ringers and all unexpired lots of Oxytocin compounded with Lactated...
http://ift.tt/2eMQIWs
Alcohol Pads or Benzalkonium Chloride Antiseptic Towelettes by Foshan Flying Medical Products: FDA Alert - Lack of Sterility Assurance and Other Quality Issues
Audience: Pharmacy, Health Professional, Patient [Posted 09/01/2017] ISSUE: The U.S. Food and Drug Administration is alerting health care professionals and patients not to use alcohol pads or benzalkonium chloride antiseptic towelettes made by...
http://ift.tt/2gxKNZ5
A gene-based test of association through an orthogonal decomposition of genotype scores
Abstract
The burden test and the sequence kernel association test (SKAT) are two popular methods for detecting association with rare variants. Treated as two different sources of association information, they are adaptively combined to form an optimal SKAT (SKAT-O) method for optimal power. We show that the burden test is part of rather than independent of the SKAT. We introduce a new test statistic that is the sum of the burden statistic and a statistic asymptotically independent of the burden statistic. The performance of this new test statistic is demonstrated through extensive simulation studies and applications to a Genetic Analysis Workshop 17 data set and the Ocular Hypertension Treatment Study data.
http://ift.tt/2gya84T
Organic Nanoparticles: Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging (Adv. Mater. 33/2017)
Runfeng Chen, Wei Huang, Kanyi Pu, and co-workers report the development of organic semiconducting nanoparticles that emit ultralong phosphorescence for afterglow optical imaging of lymph nodes in living mice, with no need for real-time light excitation, as reported in article number 1606665.
http://ift.tt/2eMFWPO
Cathodes: Rational Design of Na(Li1/3Mn2/3)O2 Operated by Anionic Redox Reactions for Advanced Sodium-Ion Batteries (Adv. Mater. 33/2017)
Inspired by in-depth understanding of the Li2MnO3 redox mechanism, Na(Li1/3Mn2/3)O2 operated by anionic redox reactions (O2−/O−: lone-pair O) is rationally designed by Maenghyo Cho, Kyeongjae Cho, and Duho Kim in article number 1701788 for high-energy-density cathodes in sodium-ion batteries (SIBs), enabling new Na(Li1/3M2/3)O2 analogues (M: transition metals featuring stabilized M4+) to break the energy-density limit of cathodes for SIBs.
http://ift.tt/2eMiUZx
Monolayers: Thermodynamically Stable Synthesis of Large-Scale and Highly Crystalline Transition Metal Dichalcogenide Monolayers and their Unipolar n–n Heterojunction Devices (Adv. Mater. 33/2017)
A novel synthesis approach for high-quality, large-scale transition-metal dichalcogenide monolayers is developed by SeungNam Cha, Jung Inn Sohn, and co-workers, as described in article number 1702206. The low supersaturation level, triggered by the evaporation of an extremely thin precursor layer, reduces the nucleation density dramatically under a thermodynamically stable environment, yielding uniform and clean large-area monolayer films. The vertically stacked heterostructured device shows a fast response time and a high photoresponsivity.
http://ift.tt/2eN1fkt
Batteries: Selenium-Doped Cathodes for Lithium–Organosulfur Batteries with Greatly Improved Volumetric Capacity and Coulombic Efficiency (Adv. Mater. 33/2017)
A novel type of selenium-doped organosulfur polymer cathode with four sulfur atoms and one selenium atom (as the doped heteroatom) in the confined structure is designed and synthesized, as described in article number 1701294 by Tao Qian, Chenglin Yan, and co-workers. The unique molecular structure through Se doping contributes greatly to the improved volumetric capacity and Coulombic efficiency for highly stable lithium organosulfur batteries.
http://ift.tt/2eMAMmO
Self-Powered Pulse Sensor for Antidiastole of Cardiovascular Disease
Cardiovascular diseases are the leading cause of death globally; fortunately, 90% of cardiovascular diseases are preventable by long-term monitoring of physiological signals. Stable, ultralow power consumption, and high-sensitivity sensors are significant for miniaturized wearable physiological signal monitoring systems. Here, this study proposes a flexible self-powered ultrasensitive pulse sensor (SUPS) based on triboelectric active sensor with excellent output performance (1.52 V), high peak signal-noise ratio (45 dB), long-term performance (107 cycles), and low cost price. Attributed to the crucial features of acquiring easy-processed pulse waveform, which is consistent with second derivative of signal from conventional pulse sensor, SUPS can be integrated with a bluetooth chip to provide accurate, wireless, and real-time monitoring of pulse signals of cardiovascular system on a smart phone/PC. Antidiastole of coronary heart disease, atrial septal defect, and atrial fibrillation are made, and the arrhythmia (atrial fibrillation) is indicative diagnosed from health, by characteristic exponent analysis of pulse signals accessed from volunteer patients. This SUPS is expected to be applied in self-powered, wearable intelligent mobile diagnosis of cardiovascular disease in the future.
A flexible self-powered ultrasensitive pulse sensor (SUPS) based on a triboelectric active sensor is proposed. SUPS can provide accurate, wireless, and real-time monitoring of pulse signals of cardiovascular system on a smart phone/PC. Different types of cardiovascular patients are indicative diagnosed from health. This SUPS is expected to be applied in intelligent mobile diagnosis of cardiovascular disease in the future.
http://ift.tt/2gq4PB9
Ultrasensitive and Fast All-Inorganic Perovskite-Based Photodetector via Fast Carrier Diffusion
Low trap-state density, high carrier mobility, and efficient charge carrier collection are key parameters for photodetectors with high sensitivity and fast response time. This study demonstrates a simple solution growth method to prepare CsPbBr3 microcrystals (MCs) with low trap-state density. Time-dependent photoluminescence study with one-photon excitation (OPE) and two-photon excitation (TPE) indicates that CsPbBr3 MCs exhibit fast carrier diffusion with carrier mobility over 100 cm2 V−1 S−1. Furthermore, CsPbBr3 MC-based photodetectors with high charge carriers' collection efficiency are fabricated. Such photodetectors show ultrahigh responsivity (R) up to 6 × 104 A W−1 with OPE and high R up to 6 A W−1 with TPE. The R for OPE is over one order of magnitude higher (the R for TPE is three orders of magnitude higher) than that of previously reported all-inorganic perovskite-based photodetectors. Moreover, the photodetectors exhibit fast response time of ≈1 ms, which corresponds to a gain ≈105 and a gain- bandwidth product of 108 Hz for OPE (a gain ≈103 and a gain-bandwidth product of 106 Hz for TPE).
CsPbBr3 microcrystal (MC)-based photodetectors exhibit ultrahigh responsivity (R) up to 6 × 104 A W−1 with one-photon excitation and R = 6 A W−1 with two-photon excitation. The photodetectors also exhibit fast response time of ≈1 ms. The sensitive and fast photoresponse is ascribed to the large absorption coefficient, low trap-state density, and high carrier mobility of CsPbBr3 MCs.
http://ift.tt/2gv7Jbo
Inverse relationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis
Abstract
Introduction
Ki67 is a prognostic marker in early breast cancer, but its real usefulness remains controversial. The standard cut-off values for Ki67 have not been universally accepted and different values may be used depending on the type of biopsy (fine needle biopsy versus surgical specimen biopsy). The objective of this study was to evaluate the prognostic significance of Ki67 and to determine the most accurate prognostic cut-off.
Materials and methods
495 tissue samples from patients with luminal tumours who underwent breast surgery between 2005 and 2011 were collected from the Department of Pathology at Hospital de la Santa Creu i Sant Pau, Barcelona. Patients with stage IV, HER2-positive tumours or triple-negative breast carcinoma were excluded from the study. Pathology data including tumour grading and ki67 percentage were obtained retrospectively from clinical records. In all cases, the percentage of ki67 was evaluated in fine needle biopsies.
Results
In the multivariate analysis, Ki67 as a continuous variable was associated with poor overall survival (OS) and cancer-specific survival (CSS) (OS p = 0.0001, HR 1.037, CI 1.014–1.059; CSS p = 0.0001, HR 1.063, CI 1.031–1.096) (Cox regression model). CSS was poor when associated with a KI67 cut-off point >14% (p = 0.013, HR 14.85; CI 1.074–120.53) (Cox regression model). Disease-free survival (DFS) was not associated with Ki67
Conclusions
Prognosis of luminal breast carcinoma can be predicted using Ki67 as a continuous variable and a standard cut-off value of 14%. Information about the specimen type used to determine ki67 should be recorded in the pathological report.
http://ift.tt/2wummPY
Evolutionary origin of synapses and neurons – Bridging the gap
The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non-bilaterian metazoans, both with and without neurons and their closest relatives already contain many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non-bilaterian metazoans. The evolution of synapses and neurons are often discussed only from a metazoan perspective leaving a considerable gap in our understanding. By taking an integrative approach we highlight the need to consider different, but extremely relevant phyla and to include the closest unicellular relatives of metazoans, the ichthyosporeans, filastereans and choanoflagellates, to fully understand the evolutionary origin of synapses and neurons. This approach allows for a detailed understanding of when and how the first pre- and postsynaptic signaling machineries evolved.
The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Most of our knowledge and recent discussions are biased towards a metazoan perspective, leaving a considerable gap in our understanding. Recent work has now revealed important insights into the emergence and co-regulation of complex synaptic signaling machineries from studies in the closest unicellular relatives of metazoans (choanoflagellates, filastereans, and ichthyosporeans).
http://ift.tt/2eqExxL
The promise and peril of CRISPR gene drives
Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.
CRISPR-based synthetic selfish genetic elements, or gene drives, have been proposed as a means by which to genetically alter natural populations to address issues in agriculture, conservation, and public health. We describe key concepts of CRISPR gene drives and limitations that must be addressed before their use in the wild.
http://ift.tt/2iNkMWj
New on NCI’s Websites for September 2017
NCI periodically provides updates on new websites and other online content of interest to the cancer community.
http://ift.tt/2wqduwz
Soil microbial community dynamics and assembly under long-term land use change
Abstract
We evaluated the bacterial and archaeal community dynamics and assembly in soils under forest, grassland and no-till cropping, using a high throughput shotgun metagenomics approach. No significant alterations in alpha diversity were observed among different land uses, but beta diversity in grassland was lower than those observed in forest and no-till soils. Grassland communities showed assembly that predominantly followed the neutral model, i.e. high homogenizing selection with moderate dispersion, leading to biotic homogenization. Both no-till and forest soil communities were found to have assembly that predominantly followed a niche model, i.e. low rates of dispersal and weak homogenizing selection, resulting in maintenance of higher beta diversity relative to grasslands, indicating niche specialization or variable selection. Taken together, our results indicate that the patterns of assembly and their governing processes are dependent on the land use employed after deforestation, with consequences to taxa turnover and microbial functional potential.http://ift.tt/2wqzEil
Shifting Zebrafish Lethal Skeletal Mutant Penetrance by Progeny Testing
The goal of this protocol is to alter the penetrance of lethal skeletal mutant phenotypes in zebrafish by selective breeding. Lethal mutants cannot be grown to adulthood and bred themselves, therefore this protocol describes a method for tracking and selecting penetrance through multiple generations by progeny testing.
http://ift.tt/2wZ0krV
Apoptosis induced by Moringa oleifera Lam. pod in mouse colon carcinoma model
Abstract
The aim of this study was to investigate the effect of boiled Moringa oleifera Lam. pod (bMO) in colon carcinogenesis via apoptotic pathway. Four groups of mice (eight mice/group) were induced by azoxymethane (AOM, 10 mg/kg BW i.p. at the third week) followed by dextran sodium sulfate (DSS) for 7 days (2% in drinking water at the fourth week), while one negative group (n = 8) received AIN-76A basal diet without AOM/DSS induction. Positive control group received basal diet with AOM/DSS induction, whereas treatment groups received basal diet containing 1.5%, 3.0%, and 6.0% of bMO at the 5th week till 20th week after AOM/DSS inductions. Mice were sacrificed and necropsied at the end of the 20th week. The results showed tumor incidence 87.5% and multiplicity 9.5 in positive control group. Subsequently, mice that received 1.5%–6.0% bMO exhibited tumor incidences and multiplicities at 25%–75% and 1.8–8.3, respectively. Pro-apoptosis protein BAX investigated by immunohistochemistry in mice treated with 3.0% bMO was significantly higher than positive control. Anti-apoptosis protein BCL-2 showed the lowest expression in mice fed with 6.0% bMO. The BAX/BCL-2 ratio proteins and the nuclear staining were found at the highest rate in mice received 3.0% bMO. This finding suggested that the bMO exhibited potent apoptosis induction through dissimilarity of BCL-2 family protein expression, thereby decreased BCL-2 protein expression and increased the BAX protein to promote cell death. Therefore, bMO has a potential as chemotherapeutic agent in colon cancer through induction of apoptosis.
http://ift.tt/2eMvCYi
Canalization of Seasonal Phenology in the Presence of Developmental Variation: Seed Dormancy Cycling in an Annual Weed
Abstract
Variation in the developmental timing in one life stage may ramify within and across generations to disrupt optimal phenology of other life stages. By focusing on a common mechanism of developmental arrest in plants—seed dormancy—we investigated how variation in flowering time influenced seed germination behavior and identified potential processes that can lead to canalized germination behavior despite variation in reproductive timing. We quantified effects of reproductive timing on dormancy cycling by experimentally manipulating the temperature during seed maturation and the seasonal timing of seed dispersal/burial, and by assessing temperature-dependent germination of un-earthed seeds over a seasonal cycle. We found that reproductive timing, via both seed-maturation temperature and the timing of dispersal, strongly influenced germination behavior in the weeks immediately following seed burial. However, buried seeds subsequently canalized their germination behavior, after losing primary dormancy and experiencing natural temperature and moisture conditions in the field. After the complete loss of primary dormancy, germination behavior was similar across seed-maturation and dispersal treatments, even when secondary dormancy was induced. Maternal effects themselves may contribute to the canalization of germination: first, by inducing stronger dormancy in autumn-matured seeds, and second by modifying the responses of those seeds to their ambient environment. Genotypes differed in dormancy cycling, with functional alleles of known dormancy genes necessary for the suppression of germination at warm temperatures in autumn through spring across multiple years. Loss of function of dormancy genes abolished almost all dormancy cycling. In summary, effects of reproductive phenology on dormancy cycling of buried seeds were apparent only as long as seeds retained primary dormancy, and a combination of genetically imposed seed dormancy, maternally induced seed dormancy, and secondary dormancy can mitigate variation in germination behavior imposed by variation in reproductive phenology.http://ift.tt/2gvcv8L
20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells
Abstract
The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.
http://ift.tt/2gvIHsF
Stereological Estimation of Dopaminergic Neuron Number in the Mouse Substantia Nigra Using the Optical Fractionator and Standard Microscopy Equipment
http://ift.tt/2vRVs2I
Dietary fatty acid intake after myocardial infarction: a theoretical substitution analysis of the Alpha Omega Cohort [Nutritional epidemiology and public health]
Background: Replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs), especially polyunsaturated fatty acids (PUFAs), has been associated with a lower risk of ischemic heart disease (IHD). Whether this replacement is beneficial for drug-treated patients with cardiac disease is not yet clear.
Objective: In a prospective study of Dutch patients with cardiac disease (Alpha Omega Cohort), we examined the risk of cardiovascular disease (CVD) and IHD mortality when the sum of SFAs and trans fatty acids (TFAs) was theoretically replaced by total UFAs, PUFAs, or cis monounsaturated fatty acids (MUFAs).
Design: We included 4146 state-of-the-art drug-treated patients aged 60–80 y with a history of myocardial infarction (79% male patients) and reliable dietary data at baseline (2002–2006). Cause-specific mortality was monitored until 1 January 2013. HRs for CVD mortality and IHD mortality for theoretical, isocaloric replacement of dietary fatty acids (FAs) in quintiles (1–5) and continuously (per 5% of energy) were obtained from Cox regression models, adjusting for demographic factors, medication use, and lifestyle and dietary factors.
Results: Patients consumed, on average, 17.5% of energy of total UFAs, 13.0% of energy of SFAs, and <1% of energy of TFAs. During ~7 y of follow-up, 372 CVD deaths and 249 IHD deaths occurred. Substitution modeling yielded significantly lower risks of CVD mortality when replacing SFAs plus TFAs with total UFAs [HR in quintile 5 compared with quintile 1: 0.45 (95% CI: 0.28, 0.72)] or PUFAs [HR: 0.66 (95% CI: 0.44, 0.98)], whereas HRs in cis MUFA quintiles were nonsignificant. HRs were similar for IHD mortality. In continuous analyses, replacement of SFAs plus TFAs with total UFAs, PUFAs, or cis MUFAs (per 5% of energy) was associated with significantly lower risks of CVD mortality (HRs between 0.68 and 0.75) and IHD mortality (HRs between 0.55 and 0.70).
Conclusion: Shifting the FA composition of the diet toward a higher proportion of UFAs may lower CVD mortality risk in drug-treated patients with cardiac disease. This study was registered at clinicaltrials.gov as NCT03192410.
http://ift.tt/2gpTu3X
Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and {beta} cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial [Gene-nutrient interactions]
Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.
Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss.
Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20–25% fat, 15% protein, and 60–65% carbohydrate; high-fat diet: 40–45% fat, 15% protein, and 40–45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581.
Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: –0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: –13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally (P = 0.10) and not significantly (P = 0.24) associated with insulin and HOMA-B, respectively.
Conclusion: PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281.
http://ift.tt/2evyQ5E
Determination of Inorganic Arsenic in a Wide Range of Food Matrices using Hydride Generation - Atomic Absorption Spectrometry.
The usefulness of an analytical method to determine inorganic arsenic in a wide range of food matrices is demonstrated. The method consists of selective extraction of inorganic arsenic into chloroform with a final determination by hydride generation-atomic absorption spectrometry.
http://ift.tt/2eqdZg5
Ultrasound-guided Intracardiac Injection of Human Mesenchymal Stem Cells to Increase Homing to the Intestine for Use in Murine Models of Experimental Inflammatory Bowel Diseases
Murine studies in models of colonic inflammation have demonstrated that a small percentage (1 - 5%) of mesenchymal stem cells (MSC) injected intravenously or intraperitoneally home to the inflamed colon1,2. This study shows that ultrasound-guided intracardiac injections of MSCs result in increased localization to the intestine.
http://ift.tt/2iNdORg
Value of physical tests in diagnosing cervical radiculopathy: a systematic review
Publication date: Available online 31 August 2017
Source:The Spine Journal
Author(s): Erik J Thoomes, Sarita van Geest, Danielle A van der Windt, Deborah Falla, Arianne P Verhagen, Bart W Koes, Marloes Thoomes-de Graaf, Barbara Kuijper, Wendy GM Scholten-Peeters, Carmen L Vleggeert-Lankamp
Background contextIn clinical practice, the diagnosis of cervical radiculopathy is based on information from the patient history, physical examination and diagnostic imaging. Various physical tests may be performed, but their diagnostic accuracy is unknown.PurposeTo summarize and update the evidence on diagnostic performance of tests carried out during a physical examination for the diagnosis of cervical radiculopathy.Study designReview of the accuracy of diagnostic tests.Study SampleDiagnostic studies comparing results of tests performed during a physical examination in diagnosing cervical radiculopathy with a reference standard of imaging or surgical findings.Outcome measuresSensitivity, specificity, likelihood ratios are presented, together with pooled results for sensitivity and specificity.MethodsA literature search up to March 2016 was performed in CENTRAL, PubMed (MEDLINE), EMBASE, CINAHL, Web of Science and Google Scholar. Methodological quality of studies was assessed using the QUADAS-2.ResultsFive diagnostic accuracy studies were identified. Only Spurling's test was evaluated in more than one study, showing high specificity ranging from 0.89-1.00 (95%CI: 0.59-1.00); sensitivity varied from 0.38-0.97 (95%CI: 0.21-0.99). No studies were found that assessed the diagnostic accuracy of widely used neurological tests such as key muscle strength, tendon reflexes and sensory impairments.ConclusionsThere is limited evidence for accuracy of physical examination tests for the diagnosis of cervical radiculopathy. When consistent with the patient history, clinicians may use a combination of Spurling's, axial traction and an Arm Squeeze test to increase the likelihood of a cervical radiculopathy; whereas a negative combined neurodynamic testing and an Arm Squeeze test could be used to rule out the disorder.
http://ift.tt/2eq6Yfu
Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma
Abstract
Background
Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker.
Methods
We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection.
Results
GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences.
Conclusions
Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.
http://ift.tt/2gvMMNu
A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients
Abstract
Background
Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients.
Methods
In an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693–704, 2006).
Results
The evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82–1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04–3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21–45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP.
Conclusions
T4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature.
http://ift.tt/2gwPq5A
Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
Abstract
Background
MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer.
Methods
Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed.
Results
Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs.
Conclusions
There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.
http://ift.tt/2eMbN3j
Suicide and all-cause mortality in Swedish deployed military veterans: a population-based matched cohort study
Objective
To investigate suicide and mortality risk in deployed military veterans versus non-deployed comparators who had gone through military conscription testing.
DesignPopulation-based matched cohort study.
SettingSweden.
ParticipantsParticipants were identified from the Military Service Conscription Register and deployment status from the Swedish Military Information Personnel Register. Of 1.9 million conscripts, 21 721 had deployed at some time between 1990 and 2013 (deployed military veterans). Non-deployed comparators were matched to deployed military veterans in two ways: (1) by cognitive ability, psychological assessment, mental health, body mass index, sex, birth-year and conscription-year (carefully matched), with further adjustment for exercise capacity and suicide attempt history; and (2) by sex, birth-year and conscription-year (age- and sex-matched).
Main outcomeSuicide retrieved from the Swedish National Patient and Causes of Death Register until 31 December 2013.
ResultsDuring a median follow-up of 12 years, 39 and 211 deaths by suicide occurred in deployed military veterans (n=21 627) and carefully matched non-deployed comparators (n=107 284), respectively (15 vs 16/100 000 person-years; adjusted HR (aHR) 1.07; 95% CI 0.75 to 1.52; p=0.72) and 329 in age- and sex-matched non-deployed comparators (n=108 140; 25/100 000 person-years; aHR 0.59; 95% CI 0.42 to 0.82; p=0.002). There were 284 and 1444 deaths by suicide or attempted suicides in deployed military veterans and carefully matched non-deployed comparators, respectively (109 vs 112; aHR 0.99; 95% CI 0.88 to 1.13; p=0.93) and 2061 in age- and sex-matched non-deployed comparators (158; aHR 0.69; 95% CI 0.61 to 0.79; p<0.001). The corresponding figures for all-cause mortality for carefully matched non-deployed comparators were 159 and 820 (61 vs 63/100 000 person-years; aHR 0.97; 95% CI 0.82 to 1.15; p=0.71) and 1289 for age- and sex-matched non-deployed comparators (98/100 000 person-years; aHR 0.62; 95% CI 0.52 to 0.73; p<0.001).
ConclusionDeployed military veterans had similar suicide and mortality risk as non-deployed comparators after accounting for psychological, psychiatric and physical factors. Studies of mental health in deployed veterans need to adjust for more factors than age and sex for comparisons to be meaningful.
http://ift.tt/2gwihHm
Patients and nurses views on providing psychological support within cardiac rehabilitation programmes: a qualitative study
Objective
To explore patients' and nurses' views on the feasibility and acceptability of providing psychological care within cardiac rehabilitation services.
DesignIn-depth interviews analysed thematically.
Participants18 patients and 7 cardiac nurses taking part in a pilot trial (CADENCE) of an enhanced psychological care intervention delivered within cardiac rehabilitation programmes by nurses to patients with symptoms of depression.
SettingCardiac services based in the South West of England and the East Midlands, UK.
ResultsPatients and nurses viewed psychological support as central to good cardiac rehabilitation. Patients' accounts highlighted the significant and immediate adverse effect a cardiac event can have on an individual's mental well-being. They also showed that patients valued nurses attending to both their mental and physical health, and felt this was essential to their overall recovery. Nurses were committed to providing psychological support, believed it benefited patients, and advocated for this support to be delivered within cardiac rehabilitation programmes rather than within a parallel healthcare service. However, nurses were time-constrained and found it challenging to provide psychological care within their existing workloads.
ConclusionsBoth patients and nurses highly value psychological support being delivered within cardiac rehabilitation programmes but resource constraints raise barriers to implementation. Consideration, therefore, should be given to alternative forms of delivery which do not rely solely on nurses to enable patients to receive psychological support during cardiac rehabilitation.
Trial registration numberISCTRN34701576.
http://ift.tt/2gwiXwj
Epidemiology of competence: a scoping review to understand the risks and supports to competence of four health professions
Objectives
This study examined the risks and supports to competence discussed in the literature related to occupational therapists, pharmacists, physical therapists and physicians, using epidemiology as a conceptual model.
DesignArticles from a scoping literature review, published from 1975 to 2014 inclusive, were included if they were about a risk or support to the professional or clinical competence of one of four health professions. Descriptive and regression analyses identified potential associations between risks and supports to competence and the location of study, type of health profession, competence life-cycle and the domain(s) of competence (organised around the CanMEDS framework).
ResultsA total of 3572 abstracts were reviewed and 943 articles analysed. Most focused on physicians (n=810, 86.0%) and 'practice' (n=642, 68.0%). Fewer articles discussed risks to competence (n=418, 44.3%) than supports (n=750, 79.5%). The top four risks, each discussed in over 15% of articles, were: transitions in practice, being an international graduate, lack of clinical exposure/experience (ie, insufficient volume of procedures or patients) and age. The top two supports (over 35%) were continuing education participation and educational information/programme features. About 60% of all the articles discussed medical expert and about 25% applied to all roles. Articles focusing on residents had a greater probability of reporting on risks.
ConclusionsArticles about physicians were dominant. The majority of articles were written in the last decade and more discussed supports than risks to competence. An epidemiology-based conceptual model offers a helpful organising framework for exploring and explaining the competence of health professions.
http://ift.tt/2eLHwRY
Admission to psychiatric hospital for mental illnesses 2 years prechildbirth and postchildbirth in Scotland: a health informatics approach to assessing mother and child outcomes
Objective
To identify factors associated with: admission to a specialist mother and baby unit (MBU) and the impact of perinatal mental illness on early childhood development using a data linkage approach in the 2 years prechildbirth and postchildbirth.
MethodsScottish maternity records (SMR02) were linked to psychiatric hospital admissions (SMR04). 3290 pregnancy-related psychiatric admissions for 1730 women were assessed. To investigate factors associated with MBU admission, the group of mothers admitted to an MBU were compared with those admitted to general psychiatric wards. To assess the impact of perinatal mental illness on early child development, a pragmatic indicator for 'at potential risk of adversity', defined as a child who was recorded as requiring intensive treatment at any time under the health plan indicators (HPI) and/or who had no record of completing three doses of the 5-in-1 vaccine by 12 months was generated. Logistic regression models were used to describe the association between each variable and the risk of admission between those with a history of prior psychiatric admission and those without.
ResultsWomen admitted to an MBU were significantly more likely to be admitted with non-affective psychosis (OR=1.97, 95% CI 1.22 to 3.18), affective psychosis (OR=2.44, 95% CI 1.37 to 4.33) and non-psychotic depressive episodes (OR=1.93, 95% CI 1.42 to 2.63). They were less likely to come from deprived areas (OR=0.68 95% CI 0.49 to 0.93). Women with a previous history of psychiatric admission were significantly more likely to be located in the two most deprived quintiles. Almost one-third (29%) of children born to mothers with a pregnancy-related psychiatric admission were assessed as 'at potential risk of adversity.'
ConclusionsA health informatics approach has potential for improving understanding of social and clinical factors, which contribute to the outcomes of perinatal mental illness, as well as potential adverse developmental outcomes for offspring.
http://ift.tt/2gwInd8
Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis
Objectives
Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics.
Setting, participants and outcome measuresWe searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses.
ResultsThe pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses.
ConclusionsOur systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.
http://ift.tt/2gwTiDu
Is there evidence that the yearly numbers of children newly certified with sight impairment in England and Wales has increased between 1999/2000 and 2014/2015? A cross-sectional study
Objectives
To use routine data capture from hospitals in England and Wales to identify whether there has been an increase in the annual numbers of children newly certified sight impaired in England and Wales between 1999/2000 and 2014/2015 and to examine causes of certifiable sight impairment in children certified in 2014/2015.
DesignA cross-sectional study including an analysis of all certificates of vision impairment completed in hospitals in England and Wales each year between 2007/2008 and 2014/2015 and all certificates completed in hospitals in England and Wales in 1999/2000.
ParticipantsCertificates for all individuals aged 16 years or less at the time of certification in England and Wales for each financial year between 1 April 2007 and the 31 March 2015 and for individuals aged 15 years or less for the year ending 31 March 2000. We obtained information on the main cause of certifiable sight loss for all children certified in 2014/2015. We estimated crude and sex specific incidence estimates with 95% confidence intervals computed by Byars method.
ResultsIn 1999/2000, the estimated incidence (95 % CI) of certification was 8.2 (7.7 to 8.8) per 1 00 000. In 2007/2008, the estimated incidence was statistically significantly higher at 10.1 (9.5 to 10.7). Since then a trend of increasing incidence with time has been observed until 2014/2015 when an estimated incidence of 13.3 (12.6 to 14.0) was observed. Hereditary retinal dystrophies, cerebral visual impairment and nystagmus were the most common single causes of certifiable sight impairment in children in 2014/2015.
ConclusionOur findings show that in England and Wales there has been an increase in the number of children newly certified sight impaired by consultant ophthalmologists since 1999/2000. This mirrors our previous findings based on data originating within social service departments.
http://ift.tt/2gwILZ8
Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale
Introduction
Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh.
Methods and analysisThe study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants' source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants.
Ethics and disseminationThe study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals.
Trial registration numberNCT02746003; Pre-results.
http://ift.tt/2gw4FM4
Interprofessional team assessments of the patient safety climate in Swedish operating rooms: a cross-sectional survey
Background
A positive patient safety climate within teams has been associated with higher safety performance. The aim of this study was to describe and compare attitudes to patient safety among the various professionals in surgical teams in Swedish operating room (OR) departments. A further aim was to study nurse managers in the OR and medical directors' estimations of their staffs' attitudes to patient safety.
MethodsA cross-sectional survey with the Safety Attitudes Questionnaire (SAQ) was used to elicit estimations from surgical teams. To evoke estimations from nurse managers and medical directors about staff attitudes to patient safety, a short questionnaire, based on SAQ, was used. Three OR departments at three different hospitals in Sweden participated. All licensed practical nurses (n=124), perioperative nurses (n=233), physicians (n=184) and their respective manager (n=22) were invited to participate.
ResultsMean percentage positive scores for the six SAQ factors and the three professional groups varied, and most factors (safety climate, teamwork climate, stress recognition, working conditions and perceptions of management), except job satisfaction, were below 60%. Significantly lower mean values were found for perioperative nurses compared with physicians for perceptions of management (56.4 vs 61.4, p=0.013) and working conditions (63.7 vs 69.8, p=0.007). Nurse managers and medical directors' estimations of their staffs' ratings of the safety climate cohered fairly well.
ConclusionsThis study shows variations and some weak areas for patient safety climate in the studied ORs as reported by front-line staff and acknowledged by nurse managers and medical directors. This finding is a concern because a weak patient safety climate has been associated with poor patient outcomes. To raise awareness, managers need to support patient safety work in the OR.
http://ift.tt/2eLHEAT
Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial
Introduction
Available data show that approximately 8%–18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy.
Methods and analysisThis is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population.
Ethics and disseminationAll participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China.
Trial registrationClinicalTrials.gov ID: NCT02900729; pre-results.
http://ift.tt/2gvFpWk
Development and validation of the Fracture Risk Scale (FRS) that predicts fracture over a 1-year time period in institutionalised frail older people living in Canada: an electronic record-linked longitudinal cohort study
Objectives
To develop and validate our Fracture Risk Scale (FRS) over a 1-year time period, using the long-term care (LTC) Resident Assessment Instrument Minimum Data Set Version 2.0 (RAI-MDS 2.0).
DesignA retrospective cohort study.
SettingLTC homes in Ontario, Canada.
ParticipantsOlder adults who were admitted to LTC and received a RAI-MDS 2.0 admission assessment between 2006 and 2010.
ResultsA total of 29 848 LTC residents were enrolled in the study. Of these 22 386 were included in the derivation dataset and 7462 individual were included in the validation dataset. Approximately 2/3 of the entire sample were women and 45% were 85 years of age or older. A total of 1553 (5.2%) fractures were reported over the 1-year time period. Of these, 959 (61.8%) were hip fractures. Following a hip fracture, 6.3% of individuals died in the emergency department or as an inpatient admission and did not return to their LTC home. Using decision tree analysis, our final outcome scale had eight risk levels of differentiation. The percentage of individuals with a hip fracture ranged from 0.6% (lowest risk level) to 12.6% (highest risk level). The area under the curve of the outcome scale was similar for the derivation (0.67) and validation (0.69) samples, and the scale exhibited a good level of consistency.
ConclusionsOur FRS predicts hip fracture over a 1-year time period and should be used as an aid to support clinical decisions in the care planning of LTC residents. Future research should focus on the transformation of our scale to a Clinical Assessment Protocol and to assess the FRS in other healthcare settings.
http://ift.tt/2eM4qsx
Common evidence gaps in point-of-care diagnostic test evaluation: a review of horizon scan reports
Objective
Since 2008, the Oxford Diagnostic Horizon Scan Programme has been identifying and summarising evidence on new and emerging diagnostic technologies relevant to primary care. We used these reports to determine the sequence and timing of evidence for new point-of-care diagnostic tests and to identify common evidence gaps in this process.
DesignSystematic overview of diagnostic horizon scan reports.
Primary outcome measuresWe obtained the primary studies referenced in each horizon scan report (n=40) and extracted details of the study size, clinical setting and design characteristics. In particular, we assessed whether each study evaluated test accuracy, test impact or cost-effectiveness. The evidence for each point-of-care test was mapped against the Horvath framework for diagnostic test evaluation.
ResultsWe extracted data from 500 primary studies. Most diagnostic technologies underwent clinical performance (ie, ability to detect a clinical condition) assessment (71.2%), with very few progressing to comparative clinical effectiveness (10.0%) and a cost-effectiveness evaluation (8.6%), even in the more established and frequently reported clinical domains, such as cardiovascular disease. The median time to complete an evaluation cycle was 9 years (IQR 5.5–12.5 years). The sequence of evidence generation was typically haphazard and some diagnostic tests appear to be implemented in routine care without completing essential evaluation stages such as clinical effectiveness.
ConclusionsEvidence generation for new point-of-care diagnostic tests is slow and tends to focus on accuracy, and overlooks other test attributes such as impact, implementation and cost-effectiveness. Evaluation of this dynamic cycle and feeding back data from clinical effectiveness to refine analytical and clinical performance are key to improve the efficiency of point-of-care diagnostic test development and impact on clinically relevant outcomes. While the 'road map' for the steps needed to generate evidence are reasonably well delineated, we provide evidence on the complexity, length and variability of the actual process that many diagnostic technologies undergo.
http://ift.tt/2eLKC8x
Psychological distress and quality of life: rationale and protocol of a prospective cohort study in a rural district in Bangaladesh
Introduction
A significant proportion of the global burden of disease has been attributed to mental and behavioural disorders. People with mental disorders (MDs) have lower levels of health-related quality of life than those without MDs. Several studies have shown that in low-resource countries, a range of social determinants including poor health literacy is critical in the epidemiological transition of disease outcome. There is a lack of evidence of MDs literacy, the prevalence and risk factors of common mental health conditions, or any validated instruments to measure psychological distress or evaluate the quality of life in rural areas of Bangladesh.
AimsThe aims of this study are: (1) report the awareness, knowledge, attitudes and practice (KAP) of MDs; (2) estimate the prevalence of and risk factors for psychological distress; (3) measure association of psychological distress and other socio-demographic factors with quality of life and (4) test the feasibility to use Kessler 10-item (K10) and WHO Quality Of Life-BREF (WHOQOL-BREF) questionnaires in rural Bangladesh for measuring psychological distress and quality of life.
Methods and analysisA sample of 1500 adults aged 18–59 years and 1200 older adults aged 60–90 years will be interviewed from a multistage cluster random sample. Each participant will go through a face-to-face interview to assess their awareness and KAP of MDs. Information about the participant's sociodemographic and socioeconomic status will be collected along with the psychological distress (K10) and quality of life (WHOQOL-BREF) questionnaires. Internal consistency, validity, reliability and item discrimination of K10 and WHOQOL-BREF instruments will be determined by using Rasch analysis and regression techniques.
Ethics and disseminationHuman Ethics Approval was received from the Swinburne University of Technology Human Ethics Committee. Results of this research will be disseminated via scientific forums including peer-reviewed publications and presentations at national and international conferences.
http://ift.tt/2eLO9E6
Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol
Introduction
The majority of patients with perihilar cholangiocarcinoma (PHC) has locally advanced disease or distant lymph node metastases on presentation or exploratory laparotomy, which makes them not eligible for resection. As the prognosis of patients with locally advanced PHC or lymph node metastases in the palliative setting is significantly better compared with patients with organ metastases, ablative therapies may be beneficial. Unfortunately, current ablative options are limited. Photodynamic therapy causes skin phototoxicity and thermal ablative methods, such as stereotactic body radiation therapy and radiofrequency ablation, which are affected by a heat/cold-sink effect when tumours are located close to vascular structures, such as the liver hilum. These limitations may be overcome by irreversible electroporation (IRE), a relatively new ablative method that is currently being studied in several other soft tissue tumours, such as hepatic and pancreatic tumours.
Methods and analysisIn this multicentre phase I/II safety and feasibility study, 20 patients with unresectable PHC due to vascular or distant lymph node involvement will undergo IRE. Ten patients who present with unresectable PHC will undergo CT-guided percutaneous IRE, whereas ultrasound-guided IRE will be performed in 10 patients with unresectable tumours detected at exploratory laparotomy. The primary outcome is the total number of clinically relevant complications (Common Terminology Criteria for Adverse Events, score of≥3) within 90 days. Secondary outcomes include quality of life, tumour response, metal stent patency and survival. Follow-up will be 2 years.
Ethics and disseminationThe protocol has been approved by the local ethics committees. Data and results will be submitted to a peer-reviewed journal.
ConclusionThe Ablation with irreversible eLectroportation in Patients with Advanced perihilar CholangiocarcinomA (ALPACA) study is designed to assess the feasibility of IRE for advanced PHC. The main purpose is to inform whether a follow-up trial to evaluate safety and effectiveness in a larger cohort would be feasible.
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Design and validation of a clinical scale for prehospital stroke recognition, severity grading and prediction of large vessel occlusion: the shortened NIH Stroke Scale for emergency medical services
Objective
To develop an NIH Stroke Scale (NIHSS)-compatible, all-in-one scale for rapid and comprehensive prehospital stroke assessment including stroke recognition, severity grading and progression monitoring as well as prediction of large vessel occlusion (LVO).
MethodsEmergency medical services (EMS) personnel and stroke physicians (n=326) rated each item of the NIHSS regarding suitability for prehospital use; best rated items were included. Stroke recognition was evaluated retrospectively in 689 consecutive patients with acute stroke or stroke mimics, prediction of LVO in 741 consecutive patients with ischaemic stroke with acute vessel imaging independent of admission NIHSS score.
ResultsNine of the NIHSS items were rated as 'suitable for prehospital use.' After excluding two items in order to increase specificity, the final scale (termed shortened NIHSS for EMS, sNIHSS-EMS) consists of 'level of consciousness', 'facial palsy', 'motor arm/leg', 'sensory', 'language' and 'dysarthria'. Sensitivity for stroke recognition of the sNIHSS-EMS is 91% (95% CI 86 to 94), specificity 52% (95% CI 47 to 56). Receiver operating curve analysis revealed an optimal cut-off point for LVO prediction of ≥6 (sensitivity 70% (95% CI 65 to 76), specificity 81% (95% CI 76 to 84), positive predictive value 70 (95% CI 65 to 75), area under the curve 0.81 (95% CI 0.78 to 0.84)). Test characteristics were non-inferior to non-comprehensive scales.
ConclusionsThe sNIHSS-EMS may overcome the sequential use of multiple emergency stroke scales by permitting parallel stroke recognition, severity grading and LVO prediction. Full NIHSS-item compatibility allows for evaluation of stroke progression starting at the prehospital phase.
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Labtracker+, a medical smartphone app for the interpretation of consecutive laboratory results: an external validation study
Objectives
When monitoring patients over time, clinicians may struggle to distinguish 'real changes' in consecutive blood parameters from so-called natural fluctuations. In practice, they have to do so by relying on their clinical experience and intuition. We developed Labtracker+, a medical app that calculates the probability that an increase or decrease over time in a specific blood parameter is real, given the time between measurements.
DesignWe presented patient cases to 135 participants to examine whether there is a difference between medical students, residents and experienced clinicians when it comes to interpreting changes between consecutive laboratory results. Participants were asked to interpret if changes in consecutive laboratory values were likely to be 'real' or rather due to natural fluctuations. The answers of the study participants were compared with the calculated probabilities by the app Labtracker+ and the concordance rates were assessed.
Setting and participantsMedical students (n=92), medical residents from the department of internal medicine (n=19) and internists (n=24) at a Dutch University Medical Centre.
Primary and secondary outcome measuresConcordance rates between the study participants and the calculated probabilities by the app Labtracker+ were compared. Besides, we tested whether physicians with clinical experience scored better concordance rates with the app Labtracker+ than inexperienced clinicians.
ResultsMedical residents and internists showed significantly better concordance rates with the calculated probabilities by the app Labtracker+ than medical students, regarding their interpretation of differences between consecutive laboratory results (p=0.009 and p<0.001, respectively).
ConclusionThe app Labtracker+ could serve as a clinical decision tool in the interpretation of consecutive laboratory test results and could contribute to rapid recognition of parameter changes by physicians.
http://ift.tt/2eLAiO0
ZOLL announces call for presentations for Summit 2018
CHELMSFORD, Mass.— ZOLL® Medical Corporation, an Asahi Kasei Group Company that manufactures medical devices and related software solutions, today announced the call for presentations for SUMMIT 2018, which will take place in Denver, Colorado, May 8-10, 2018. Fire and EMS professionals who are interested in speaking should visit the Summit Presenter Page to review the guidelines and submit ...
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A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men
Abstract
Purpose
This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males.
Methods
In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration–time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (C max). Secondary endpoints included safety and immunogenicity.
Results
AUCinf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUCinf, respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUCinf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected.
Conclusions
This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.
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A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1403-1411, September 2017.
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Environmental Health: Lessons from the Past and Looking to the Future
http://ift.tt/2wpjKoj
Clarity on Endpoints for Clinical Trials in Idiopathic Pulmonary Fibrosis
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Procalcitonin Test Availability: A Survey of Acute Care Hospitals in Massachusetts
http://ift.tt/2wpqMZX
Hospital Variation in Do-Not-Resuscitate Orders and End-of-Life Healthcare Use in the United States
http://ift.tt/2wpFgcv
Relationship between Race and the Effect of Fluids on Long-term Mortality after Acute Respiratory Distress Syndrome. Secondary Analysis of the National Heart, Lung, and Blood Institute Fluid and Catheter Treatment Trial
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1443-1449, September 2017.
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Suspect the Unexpected: A 45-Year-Old Man with Fevers, Rash, and Multiorgan Failure
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Satori: Awakening to Outcomes That Matter: The Impact of Social Support in Chronic Obstructive Pulmonary Disease
http://ift.tt/2vQD6z5
Reply: Unilateral Pulmonary Edema after Visiting High Altitude
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1492-1493, September 2017.
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Tracheobronchomalacia Is Associated with Increased Morbidity in Bronchopulmonary Dysplasia
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1428-1435, September 2017.
http://ift.tt/2vQkUWr
Supplemental Oxygen in Interstitial Lung Disease: An Art in Need of Science
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1373-1377, September 2017.
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Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1395-1402, September 2017.
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Association between Social Support and Self-Care Behaviors in Adults with Chronic Obstructive Pulmonary Disease
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1419-1427, September 2017.
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Shedding Light on Incidental Findings on Low-Dose Lung Cancer Screening Chest Computed Tomography
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Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease, a Precursor for Epithelial Cancers: Understanding and Translation to Early Therapy
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1491-1492, September 2017.
http://ift.tt/2woXwTc
Another Brick in the Wall: Lung Clearance Index and Lower Airways Pathology in Preschool Cystic Fibrosis
http://ift.tt/2vQW08N
Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis
Annals of the American Thoracic Society, Volume 14, Issue 9, Page 1436-1442, September 2017.
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Italian consensus on diagnosis and management of Barrett’s Esophagus
Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE.
http://ift.tt/2ev68S6
Prenatal Risk Factors for PHACE Syndrome: A Study Using the PHACE Syndrome International Clinical Registry and Genetic Repository
The cause of PHACE syndrome is unknown. In a study of 218 patients, we examined potential prenatal risk factors for PHACE syndrome. Rates of pre-eclampsia and placenta previa in affected individuals were significantly greater than in the general population. No significant risk factor differences were detected between male and female subjects.
http://ift.tt/2goV3Po
Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers
To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth.
http://ift.tt/2evnAGr
Association of covered metallic stents with cholecystitis and stent migration in malignant biliary stricture
ERCP with self-expandable metallic stent (SEMS) placement provides reliable and durable relief of malignant biliary obstruction. Our objective was to compare efficacy and adverse outcomes between uncovered SEMSs (USEMSs) and covered SEMSs (CSEMSs).
http://ift.tt/2eLu2Ga
Metal Stents Versus Plastic Stents for the Management of Pancreatic Walled-Off Necrosis: A Systematic Review and Meta-Analysis
Endoscopic transluminal drainage of symptomatic walled-off necrosis (WON) is a good management option, although the optimal choice of drainage site stent is unclear. We performed a systematic review and meta-analysis to compare metal stents (MSs) and plastic stents (PSs) in terms of WON resolution, likelihood of resolution after one procedure, and adverse events.
http://ift.tt/2gv1MeC
New Research From Clinical Psychological Science
Read about the latest research published in Clinical Psychological Science:
The Diagnosis of Mental Disorders Is Influenced by Automatic Causal Reasoning
Amanda Flores, Pedro L. Cobos, and York Hagmayer
Clinicians' diagnoses can be influenced by causal assumptions they make about the relationships between symptoms. The causal-status hypothesis posits that causally central symptoms (those that affect other symptoms) are given more weight in diagnoses than peripheral symptoms (those that do not affect other symptoms). In contrast, the causal-model theory of categorization posits that diagnoses are influenced by whether observed patterns of symptoms match expected patterns of symptoms. In a test of these two theories, psychology students trained in clinical psychology read short clinical reports describing a preliminary diagnosis and three symptoms (S1, S2, and S3). The symptoms were chosen such that they represented part of a causal chain, with S1 leading to S2, and S2 leading to S3. The researchers manipulated causal coherence by informing participants about the absence of one of the three symptoms. The researchers analyzed the amount of time it took participants to read each sentence of the vignette. Reading times were found to be slower when consequences of presented symptoms were missing or effects of absent symptoms were present, a finding supportive of the causal-model theory of categorization.
One or Multiple Complicated Grief(s)? The Role of Kinship on Grief Reactions
Manuel Fernández-Alcántara and Emmanuelle Zech
Complicated grief (CG) is characterized by intense and prolonged separation anxiety, feelings of yearning, and difficulties going on living. The researchers examined whether CG is similar for people with different relationships to the deceased by having participants who had recently lost a family member (e.g., spouse, child, grandparent, sibling) complete assessments of CG. The researchers found that profiles of grief reactions varied based on the kinship relationship of the participant to the deceased. For example, the death of a child or spouse induced levels of grief that were greater than those arising as a result of the death of other types of kin. The authors suggest that kinship may be a major predictor of CG and should be potentially considered as a core variable in future CG models.
Hannah R. Snyder, Benjamin L. Hankin, Curt A. Sandman, Kevin Head, and Elysia P. Davis
Studies attempting to understand the neural influences of psychopathology have examined the link between gray matter volume (GMV) and various mental-health disorders; however, most studies have not shown a clear one-to-one relationship between GMV in specific brain areas and specific diagnoses. In this study, the researchers examined links between reductions in GMV and three broad psychopathologic dimensions: general psychopathology, internalizing-specific factors, and externalizing-specific factors. The GMV of children ages 6 through 10 was determined using an MRI scanner, whereas child psychopathology was assessed through parental completion of the child-behavior checklist and the child-behavior questionnaire. The general psychopathology factor was found to be associated with reduced GMV in prefrontal areas and the internalizing factor was associated with reduced GMV in limbic/paralimbic areas. After accounting for common psychopathology, no association between the externalizing factor and reduced GMV was found.
Anna Reebs, Kim Yuval, and Amit Bernstein
Models detailing — and interventions addressing — psychopathology in forcibly displaced persons often rely on research using nonrepresentative WEIRD (Western, educated, industrialized, rich, democratic) populations. The researchers examined distress and avoidance in response to emotional memory in highly traumatized refugees and asylum seekers. Sudanese refugees living in Israel were assessed for posttraumatic stress (PTS) severity before being asked to adopt either a self-immersed perspective or a self-distanced perspective while they recalled a time during which they had experienced profound sadness or fear. Participants then reported their current level of emotional distress and avoidance in response to the memory. PTS severity predicted emotional reactivity — but not avoidance — in response to remembering the distressing autobiographical memory. Additionally, those who took a self-immersed perspective experienced less avoidance – but not less emotional reactivity — in response to the distressing memory than those who took a self-distanced perspective. The authors suggest that the impact of remembering styles should be taken into account when considering treatment for psychopathology in this population and that more research is needed.
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Diagnostic exome sequencing in early-onset Parkinson's disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson's disease
Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole exome sequencing could be an efficient approach to genetic testing in PD. To evaluate its performance in early-onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD. Variants in validated and candidate disease genes and risk factors for PD and atypical Parkinson syndromes were annotated, followed by further analysis for selected variants. We detected pathogenic variants in Mendelian genes in 6.25% of cases and high-impact risk factor variants in GBA in 5% of cases, resulting in overall maximum diagnostic yield of 11.25%. One individual was compound heterozygous for variants affecting canonical splice sites in VPS13C, confirming the causal role of protein-truncating variants in this gene linked to autosomal-recessive early-onset PD. Despite the low diagnostic yield of exome sequencing in sporadic early-onset Parkinson's disease, the confirmation of the recently discovered VPS13C gene highlights its advantage over using predefined gene panels.
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Technical quality of root canal treatment performed by undergraduate students using hand instrumentation: a meta-analysis
Abstract
The technical quality of root canal treatment (RCT) may impact on the outcome. The quality of education received during undergraduate school may be linked to the quality of treatment provided in general dental practice. In this context, the aim of this systematic-review is to answer the following focused questions: 1) What is the frequency of acceptable technical quality of root fillings, assessed radiographically, performed by undergraduate students? 2) What are the most common errors assessed radiographically and reported in these treatments? For this purpose, articles that evaluated the quality of root fillings performed by undergraduate students were selected. Data was collected based on predetermined criteria. The key-features from the included studies were extracted. GRADE-tool assessed the quality of the evidence. MAStARI evaluated the methodological quality and a meta-analysis on all studies was conducted. At the end of the screening, twenty-four articles were identified. Overall frequency of acceptable technical quality of root fillings was 48%. From this total, 52% related to anterior-teeth, 49% to premolars, and 26% to molars. The main procedural errors reported were: ledge formation, furcation perforation, apical transportation, and apical perforation. The heterogeneity among the studies was high (84% to 99%). Five studies presented a high risk of bias, eight had a moderate risk, and 11 had low risk. The overall quality of evidence identified was very low. The conclusion was that technical quality of root fillings performed by undergraduate students is low, which may reveal that endodontic education has limited achievement at undergraduate level. A plan to improve the quality of root fillings, and by extrapolation the overall quality of root canal treatment, should be discussed by the staff responsible for endodontic education and training.
This article is protected by copyright. All rights reserved.
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Cytological and cytomorphometric characteristics of buccal mucosa cells from smokeless tobacco users
Abstract
Background
Use of smokeless tobacco (ST) is increasing in many communities. We investigated whether ST alters the cytological and cytomorphometric features of buccal mucosa cells.
Methods
Twenty male participants who had used Nicotiana rustica Linn.-containing ST (Maras powder) for at least 10 years, and 20 healthy male controls who did not use ST, were included in this study. After rinsing the mouth with water, samples were taken using a toothbrush from the buccal mucosa of subjects in both groups. Samples were gently spread over a glass slide. After applying a cytofixative spray, the Papanicolaou method was used to stain the slides. The presence of dysplasia, dyskeratosis, parakeratosis, hyperkeratosis, hypergranulosis, karyorrhexis, and pyknosis was evaluated by light microscopy, as were the increment amount of candida, cocco-bacillus, and Leptotrichia buccalis. Cytomorphometric analysis was performed and at least 20 cells with well-defined borders were evaluated from each slide, and the cellular diameter (CD), nuclear diameter (ND), and nucleus/cytoplasm (N/C) ratio of the cells were analyzed using a 60× objective.
Results
Other than the presence of dysplasia and candida, all measured cytological parameters were significantly higher in the ST users than in the non-ST users. Furthermore, CD was lower while nuclear/cytoplasmic ratio was higher in the ST users than in those non-ST users.
Conclusion
Cytological changes associated with the use of ST, include dyskeratosis, parakeratosis, hyperkeratosis, hypergranulosis, karyorrhexis, pyknosis together with increase in the bacterial population of cocco-bacillus and L. buccalis. There were no significant differences in patients with dysplasia in spite of reduction of CD, increased nuclear size and N/C ratio.
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A follow-up study on thyroid aspirates reported as atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for follicular neoplasm: A multicenter study from the Arabian Gulf region
Objective
This is a multicenter study which was conducted to evaluate the follow-up on thyroid aspirate cases with atypia of undetermined significance/follicular cells of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) using the Bethesda system for reporting thyroid cytology (TBSRTC).
Materials and Methods
The archival materials of all thyroid fine-needle aspirates over a 5-year period were retrieved from 3 institutions in the Arabian Gulf Region. All cytology slides and follow-up material for cases interpreted as AUS/FLUS and FN/SFN were reviewed. The revised diagnoses and follow-up were recorded. Analysis of risk of malignancy was calculated for the 2 entities.
Results
A total number of 2592 thyroid fine-needle aspirates were performed, out of which AUS/FLUS was found in 115 (4.4%) while FN/SFN in 39 (1.5%). Follow-up by surgery or repeat FNA was conducted on 42 (27%) and 10 (7%) patients on these 2 categories, respectively. The risk of malignancy was found to be 29% and 45%, respectively.
Conclusion
The risk of malignancy for AUS/FLUS and FN/SFN are 29% and 45%, respectively. This risk of malignancy in our study is on the higher range of that reported in the literature.
http://ift.tt/2gx84dp
Fine-needle aspiration biopsy of lytic bone lesions: An institution's experience
Objectives
Fine needle aspiration (FNAB) is an effective, minimally-invasive, inexpensive, diagnostic technique. The objective of this study was to evaluate the accuracy of FNAB in the diagnosis of bone lesions.
Methods
FNABs of bone lesions diagnosed at our institution over a 2-year period were retrospectively analyzed.
Results
241 samples were reviewed. Patients included 121 males and 120 females, with ages ranging from 4-95 years (mean = 66 years). Of these 241 cases, 43.2% had FNAB and 56.8% had FNAB with core needle biopsy (CNB). The cytologic diagnoses were categorized as nondiagnostic, benign, atypical, suspicious, and positive for malignant cells. Total of 84.3% of FNABs were diagnostic. Of the malignant cases, 78.5% were metastases from nonosseous primary sites, 17.1% were lymphoproliferative lesions, and 4.4% were primary bone tumors. The most common site of metastasis was the pelvic bones (43.5%) followed by the vertebral column (38.7%). Breast (21%), lung (12.7%), and prostate (11.3%) were the most common identifiable primary site in metastatic cases. FNA smears and cell blocks allowed identification of metastatic lesions in 94.3% cases with immunohistochemistry (IHC). Obtaining a concomitant CNB did not result in a statistically significant increase in overall diagnostic yields (P = .20), ascertaining presence of metastatic lesion (P = .96) or ability to identify site of primary tumor in cases of metastasis (P = .53) compared to FNAB alone. Diagnostic accuracy was improved by reviewing clinical history, performing cell block, and IHC.
Conclusions
FNAB is a reliable tool for diagnosis of bone lesions with comparable diagnostic sensitivity to CNB.
http://ift.tt/2eLruI2
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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