Τρίτη 9 Μαΐου 2017

Application of Atmospheric Pressure Photoionization H/D-exchange Mass Spectrometry for Speciation of Sulfur-containing Compounds

Abstract

Herein we report the observation of atmospheric pressure in-source hydrogen–deuterium exchange (HDX) of thiol group for the first time. The HDX for thiol group was optimized for positive atmospheric pressure photoionization (APPI) mass spectrometry (MS). The optimized HDX-MS was applied for 31 model compounds (thiols, thiophenes, and sulfides) to demonstrate that exchanged peaks were observed only for thiols. The optimized method has been successfully applied to the isolated fractions of sulfur-rich oil samples. The exchange of one and two thiol hydrogens with deuterium was observed in the thiol fraction; no HDX was observed in the other fractions. Thus, the results presented in this study demonstrate that the HDX-MS method using APPI ionization source can be effective for speciation of sulfur compounds. This method has the potential to be used to access corrosion problems caused by thiol-containing compounds.

Graphical Abstract



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Bobble-head doll syndrome in an 80-year-old man, associated with a giant arachnoid cyst of the lamina quadrigemina, treated with endoscopic ventriculocystocisternotomy and cystoperitoneal shunt

Abstract

Bobble-head doll syndrome (BHDS) is a rare entity, characterized by antero-posterior head bobbing, which is of the type "yes–yes." Less frequently, having a head movement of the type "no–no" is described. We report an unusual case of an 80-year-old man with a cystic mass of the lamina quadrigemina, extending to the posterior fossa. We conclude that ventriculocystocisternotomy associated with a cystoperitoneal shunt is an effective treatment for a symptomatic giant arachnoid cyst in the lamina quadrigemina.



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A case of refractory subgaleal hematoma in adolescence treated with aspiration and endovascular surgery

Abstract

A 14-year-old boy experienced sudden headache in the left parietal region, without any history of head trauma. Approximately 40 ml of hematoma was aspirated using a 22-gauge needle, and scalp swelling immediately disappeared. However, the swelling recurred bilaterally 2 weeks later. Left external carotid angiography revealed a reticular shadow consistent with subgaleal hematoma from a branch of bilateral superficial temporal arteries, without any arteriovenous shunts. The patient was successfully treated using the combination of hematoma aspiration and embolization of the superficial temporal artery. The combination of aspiration of hematoma and embolization may be effective for refractory non-traumatic subgaleal hematoma.



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Clival chordoma: a single-centre outcome analysis

Abstract

Background

The treatment of clival chordomas remains challenging. Total tumour resection is often impossible without hampering adjacent anatomical structures and causing functional sequelae. On the other hand, chordomas show limited response to non-surgical treatment modalities. Up to now, no well-established interdisciplinary treatment algorithms for clival chordomas exist. In this regard, we analysed the data from all patients that underwent interdisciplinary treatment for clival chordoma in our institution over the last 10 years.

Method

Retrospective report of all patients treated at the authors' institution from 2005 to 2015.

Results

Thirteen patients underwent 24 surgeries, of which 2 (8%) were gross total resections and 22 (92%) incomplete resections. Neurological deterioration, endocrinological disturbances and other surgical complications were observed in six (25%), three (13%) and nine (38%) cases, respectively. Three surgeries (13%) led to an improvement of the initial preoperative neurological condition. All patients were discussed on the interdisciplinary tumour board and all underwent one type of radiotherapy following initial surgery: proton beam in 11 cases (85%) and photon beam in two (15%) cases. In the course of their recurrent disease, three patients (23%) received systemic therapy (imatinib, pazopanib and nivolumab). One patient received a personalised cellular immunotherapy. One patient (8%) was lost to follow-up. Of the remaining 12 patients, four patients (33%) died in the period of analysis; all deaths were chordoma-related. The 5-year cumulative survival rate was 83% (52–97%, CI 95%), 5-year progression-free survival rate was 53% (26-79%, CI 95%). The eight patients (66%) still alive had favourable outcome (KPS, 90 ± 10.7%). SF36 analysis among the survivors revealed 43 points for the Physical Component Summary (12% above, 38% at and 50% below the general population norm) and 47 points for the Mental Component Summary (25% above, 38% at and 38% below).

Conclusions

Our patients show a low rate of gross total resection but an outcome well comparable to other published results. This emphasises the importance of interdispiplinary treatment strategies, with surgery supplying maximal safe resection and avoiding severe neurological deficit, allowing patients to undergo adjusted radiotherapy and other treatment options in a good condition.



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Target location after deep cerebral biopsies using low-volume air injection in 75 patients. Results and technical note

Abstract

Background

Stereotactic biopsy is a minimally invasive technique that allows brain tissue samples to be obtained with low risk. Classically, different techniques have been used to identify the biopsy site after surgery.

Objective

To describe a technique to identify the precise location of the target in the postoperative CT scan using the injection of a low volume of air into the biopsy cannula.

Methods

Seventy-five biopsies were performed in 65 adults and 10 children (40 males and 35 females, median age 51 years). Frame-based biopsy was performed in 46 patients, while frameless biopsy was performed in the remaining 29 patients. In both systems, after brain specimens had been collected and with the biopsy needle tip in the center of the target, a small volume of air (median 0.7 cm3) was injected into the site.

Results

A follow-up CT scan was performed in all patients. Intracranial air in the selected target was present in 69 patients (92%). No air was observed in two patients (air volume administered in these 2 cases was below 0.7 cm3), while in the remaining four patients blood content was observed in the target. The diagnostic yield in this series was 97.3%. No complications were found to be associated with intracranial air injection in any of the 75 patients who underwent this procedure.

Conclusions

The air-injection maneuver proposed for use in stereotactic biopsies of intracranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.



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Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol

Abstract

Background

The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

Method

A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments.

Results

More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed.

Conclusions

There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.



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Prolongiertes Weaning in der neurologisch-neurochirurgischen Frührehabilitation

Zusammenfassung

Das prolongierte Weaning von Patienten mit neurologischen oder neurochirurgischen Erkrankungen weist Besonderheiten auf, denen die Deutsche Gesellschaft für Neurorehabilitation e. V. in einer eigenen Leitlinie Rechnung trägt.

Im Hinblick auf Definitionen (z. B. Weaningerfolg und -versagen), Weaningkategorien, Pathophysiologie des Weaningversagens und allgemeine Weaningstrategien wird ausdrücklich auf die aktuelle S2k-Leitlinie der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. verwiesen.

In der neurologisch-neurochirurgischen Frührehabilitation werden Patienten mit zentralen Störungen der Atmungsregulation (z. B. Hirnstammläsionen), des Schluckaktes (neurogene Dysphagien), mit neuromuskulären Problemen (z. B. Critical-illness-Polyneuropathie, Guillain-Barre-Syndrom, Querschnittlähmungen, Myasthenia gravis) und/oder kognitiven Störungen (z. B. Bewusstseins- und Vigilanzstörungen, schwere Kommunikationsstörungen) versorgt, deren Betreuung bei der Entwöhnung von der Beatmung neben intensivmedizinischer Kompetenz auch neurologische bzw. neurochirurgische und neurorehabilitative Expertise erfordert. In Deutschland wird diese Kompetenz in Zentren der neurologisch-neurochirurgischen Frührehabilitation vorgehalten, und zwar als Krankenhausbehandlung.

Der Leitlinie liegt eine systematische Recherche von Leitliniendatenbanken und Medline zugrunde. Unter Moderation durch die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) erfolgte die Konsensfindung mittels nominalen Gruppenprozesses und Delphi-Verfahren.

In der vorliegenden Leitlinie der DGNR wird auf die strukturellen und inhaltlichen Besonderheiten der neurologisch-neurochirurgischen Frührehabilitation sowie vorhandene Studien zum Weaning in Frührehabilitationseinrichtungen eingegangen.

Adressaten der Leitlinie sind Neurologen, Neurochirurgen, Anästhesisten, Palliativmediziner, Logopäden, Intensivpflegekräfte, Ergotherapeuten, Physiotherapeuten und Neuropsychologen. Ferner richtet sich diese Leitlinie zur Information an Fachärzte für Physikalische Medizin und Rehabilitation (PMR), Pneumologen, Internisten, Atmungstherapeuten, den Medizinischen Dienst der Krankenkassen (MDK) und des Spitzenverbands Bund der Krankenkassen e. V. (MDS). Das wesentliche Ziel dieser Leitlinie ist es, den aktuellen Wissensstand zum Thema „Prolongiertes Weaning in der neurologisch-neurochirurgischen Frührehabilitation" zu vermitteln.



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Nichtmotorische Symptome beim Morbus Parkinson

Zusammenfassung

Der Morbus Parkinson ist eine neurodegenerative Erkrankung, die das periphere und zentrale Nervensystem betrifft. Neben den motorischen Symptomen tritt in allen Krankheitsphasen eine Vielzahl nichtmotorischer Störungen auf, die von hoher klinischer Relevanz sind. Besondere Beachtung finden in den letzten Jahren neuropsychiatrische und autonome Störungen. Unter den neuropsychiatrischen sind besonders die Depression, die kognitiven Einbußen sowie Psychosen und Impulskontrollstörungen zu nennen. Bezüglich der autonomen Funktion können alle Bereiche betroffen sein, wobei vor allem kardiovaskuläre, gastrointestinale und urogenitale Funktionsstörungen und Symptome zu nennen sind. Die Therapie ist schwierig und erfordert eine interdisziplinäre Herangehensweise. Auf dem Gebiet der nichtmotorischen Störungen besteht ein erheblicher diagnostischer und therapeutischer Bedarf.



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Aktuelle Empfehlungen der DGPPN für Schizophrenie-Qualitätsindikatoren

Zusammenfassung

Hintergrund

Für die Messung der Behandlungsqualität psychisch Kranker in Deutschland wurden bereits verschiedene Qualitätsindikatoren-Sets vorgeschlagen und in vereinzelten psychiatrischen Einrichtungen pilotiert. Die Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) befasst sich in einer „Task Force Qualitätsindikatoren (QI)" mit der Weiterentwicklung und praktischen Umsetzung von Qualitätsindikatoren für Schizophrenie.

Ziel der Arbeit

Das Ziel war die Auswahl von Qualitätsindikatoren für Schizophrenie, die auf andere Diagnosen übertragbar sowie für generische Erhebungen geeignet sind und ohne hohen zusätzlichen Dokumentationsaufwand gemessen werden können.

Methoden

In einem mehrstufigen Selektionsprozess wählte die DGPPN Task Force QI in Abstimmung mit dem Trialogischen Forum der DGPPN aus einem Grundbestand von 161 Qualitätsindikatoren aus dem nationalen und internationalen Raum Indikatoren aus, die sich auf wichtige Qualitätsaspekte beziehen.

Ergebnisse

Die DGPPN schlägt die folgenden zehn Indikatoren für die Messung der Versorgungsqualität bei Schizophrenie vor, die aus bestehenden Indikatoren-Sets inhaltlich adaptiert wurden: QI1 Langzeittherapie/Monitoring von Nebenwirkungen, QI2 Zwangsmaßnahmen, QI3 Anzahl der Suizide, QI4 Psychoedukativ-orientierte Angehörigengespräche, QI5 Zeitnahe ambulante Weiterbehandlung nach stationärer Entlassung, QI6 Deeskalationstraining – stationär, QI7 Diagnostik/Körperliche Untersuchung, QI8 Antipsychotische Polypharmazie, QI9 Rehabilitation/Berufliche Wiedereingliederung, QI10 Diagnostik/Funktionsfähigkeit.

Diskussion

Die hier vorgeschlagenen Qualitätsindikatoren müssten größtenteils mit Daten aus zusätzlichen Erhebungen gemessen werden. Nach Einschätzung der DGPPN Task Force QI ist dieser zusätzliche Dokumentationsaufwand leistbar, der Mehraufwand aber zusätzlich zu vergüten. In einem Machbarkeitstest sollen die Indikatoren in verschiedenen psychiatrischen Kliniken Deutschlands pilotiert werden.



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Neurologie in der Notaufnahme



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Schwindel in der Notaufnahme

Zusammenfassung

Schwindel gehört zu den häufigsten Leitsymptomen in der Notaufnahme. Die Ursachen können in drei Untergruppen eingeordnet werden: neurootologische (vestibuläre), internistische (v. a. kardiovaskuläre, metabolische) und psychiatrische Krankheitsbilder. Die diagnostische Einordnung in der Notaufnahme beruht vor allem auf einer strukturierten Anamnese (Art, Dauer, Provokationsfaktoren, Begleitsymptome), klinischen Untersuchung vestibulärer, okulomotorischer und zerebellärer Systeme (Kopfimpulstest, Nystagmus, „skew deviation", Lagerungsmanöver, Gang- und Standtests), sowie basalem Monitoring (Vitalzeichen, 12-Kanal-EKG, Labor). Bei der Differenzierung peripherer und zentraler Ursachen des akut vestibulären Syndroms ist die Überprüfung der HINTS-Trias („head impulse test", „nystagmus", „skew deviation") sowie der Blickfolge und raschen Blicksprünge (Sakkaden) diagnostisch wegweisend. Von einer unselektiven Anwendung bildgebender Verfahren wird aufgrund des geringen diagnostischen Mehrwerts abgeraten. Folgende Aspekte rechtfertigen eine kranielle Bildgebung: 1) Detektion fokal-neurologischer oder zentraler okulomotorischer und vestibulärer Zeichen im Untersuchungsbefund, 2) akute Gehunfähigkeit bei gering ausgeprägtem okulomotorischem Befund, 3) Vorhandensein mehrerer kardiovaskulärer Risikofaktoren, 4) Auftreten von Kopfschmerzen bislang nicht bekannter Qualität als Begleitsymptom. Neben der symptomatischen Therapie mit Antiemetika oder Analgetika muss zeitgleich die Ursache differenziert werden, um eine zielgerichtete Therapie zu ermöglichen. Beispiele sind die Akuttherapie bei zerebraler Ischämie, die Durchführung von Lagerungsmanövern bei gutartigem Lagerungsschwindel, die Kortikosteroidtherapie bei akuter unilateraler Vestibulopathie sowie der Ausgleich metabolischer Entgleisungen bei internistischen Krankheitsbildern.



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Onlineumfrage zur Struktur der Notfallneurologie in Deutschland 2016

Zusammenfassung

Eine erste Erhebung zur Struktur der neurologischen Notfallversorgung wurde im Jahr 2007 durchgeführt. Von der DGN-Kommission Neurologische Notfallmedizin wurde diese Erhebung nun mithilfe einer Onlineumfrage bei allen Einrichtungen mit neurologischen Abteilungen in Deutschland aktualisiert. Von Juli bis September 2016 wurden an 675 Adressaten (DGN-E-Mail-Verteiler) Onlinefragebögen versandt. Die Fragebögen wurden anonym von 32 % der insgesamt 342 neurologischen Kliniken in Deutschland beantwortet (49 % der Universitätskliniken). Neurologische Patienten stellen mit 12–16 % einen erheblichen Anteil aller Patienten in der Notaufnahme. Der Anteil der vollstationären Patienten, die über die Notaufnahmen in die Kliniken gelangen, liegt bei den angefragten Allgemeinkrankenhäusern nun bei 78 % (Median), bei den Universitätskliniken bei 52 %. Vor allem Großkliniken bevorzugen das organisatorische Modell einer interdisziplinär konservativ-chirurgischen Notaufnahme, die häufig von einem eigenen Chefarzt geleitet wird. Die neurologische Versorgung von Notfallpatienten ist in sehr heterogener Weise organisiert. Die fachliche Zuordnung von Notfallpatienten wird sehr unterschiedlich gehandhabt. Neurologische Patienten stellen weiterhin einen relevanten, eher zunehmenden Anteil aller Patienten in interdisziplinären Notaufnahmen. Die Notfallversorgung hat für die stationäre Versorgung in neurologischen Kliniken weiter an Bedeutung gewonnen. Die Kliniken haben erhebliche organisatorische Veränderungen vorgenommen. Weiterer Verbesserungsbedarf wird in der personellen Ausstattung der neurologischen und neuroradiologischen Notfallversorgung und der interdisziplinären Abstimmung gesehen. Eine eigenständige neurologische Notaufnahme wird von den Befragten abgelehnt.



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Genetische Grundlagen der bipolaren Störung

Zusammenfassung

Die bipolare Störung (BD) ist multifaktoriell verursacht, zur Entstehung tragen sowohl genetische als auch Umweltfaktoren bei. Der Durchbruch bei der Identifizierung der verantwortlichen Gene gelang mit genomweiten Assoziationsstudien (GWAS), in denen erstmals replizierbare genetische Risikovarianten für die BD gefunden wurden. Neben den durch die GWAS identifizierten häufigen genetischen Varianten mit kleinen Effekten werden auch seltene Varianten mit höherer Penetranz zur Krankheitsentstehung beitragen. So gibt es erste Hinweise darauf, dass genomische Kopienzahlvarianten mit der Entstehung der BD assoziiert sind, ihr Beitrag zur Krankheitsentstehung ist aber geringer als bei der Schizophrenie oder dem Autismus. Die wenigen bisher bei der BD durchgeführten großflächigen Sequenzierungsstudien deuten auf eine Anreicherung seltener Varianten in zuvor mit der BD assoziierten Stoffwechselwegen und Genen hin. Im Bereich der Pharmakogenetik konnte mit einer großen internationalen GWAS erstmals ein Gen identifiziert werden, welches das individuell unterschiedliche Ansprechen auf Lithium beeinflusst. Die bisher beschriebenen Risikovarianten erklären allerdings einen zu geringen Anteil der phänotypischen Varianz, als dass sie derzeit für eine individuelle Prädiktion des Erkrankungsrisikos, des Krankheitsverlaufs oder des Ansprechens auf Medikamente genutzt werden könnten. Die genetische Forschung wird in Zukunft weitere BD-assoziierte Gene identifizieren und damit das Wissen um die biologischen Grundlagen der BD entscheidend erweitern. Die genetischen Kenntnisse werden u. a. helfen, ätiologische Subgruppen sowie diagnoseübergreifende Krankheitsmechanismen zu identifizieren.



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Kopfschmerz in der Notaufnahme

Zusammenfassung

Kopfschmerz ist eines der häufigsten Leitsymptome für eine Vorstellung in der Notaufnahme. In diesem Artikel soll ein Algorithmus vorgestellt werden, wie in einer solchen Situation vorgegangen werden kann. Grundlage ist eine ausführliche Anamnese des aktuellen Kopfschmerzes mit besonderem Fokus auf Dynamik, Phänotyp und Triggerfaktoren sowie einer eventuell vorbestehenden Kopfschmerzerkrankung. Warnzeichen (sog. „red flags") müssen explizit erfragt werden. In Kombination mit einer klinischen Untersuchung (Vitalparameter, neurologischer Status, fokussierte HNO- und augenärztliche Befunde) werden Hypothesen generiert, die ggf. mittels erweiterter Diagnostik, insbesondere Bildgebung, Labor, Liquoruntersuchung und Duplexsonographie überprüft werden müssen. Ein sekundärer Kopfschmerz sollte symptomatisch und wenn möglich ursächlich behandelt werden. Ergeben sich keine Hinweise auf einen sekundären Kopfschmerz, sollte eine möglichst spezifische primäre Kopfschmerzdiagnose gestellt werden, die entsprechend zu behandeln ist. Ist eine Entlassung möglich, empfehlen wir eine ambulante Verlaufskontrolle, um den Verlauf sekundärer Kopfschmerzen bzw. deren Ursache zu verfolgen, und um bei primären Kopfschmerzen durch eine Prophylaxe und adäquate Akuttherapie wiederholte Notfallvorstellungen zu verhindern.



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Mitteilungen der DGPPN



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Artifizielle Störungen

Zusammenfassung

Patienten mit artifiziellen Störungen täuschen körperliche oder seelische Symptome vor, aggravieren sie oder fügen sie sich selbst zu, um Ärzten gegenüber Krankheiten zu präsentieren. Die Tatsache der Täuschung ist den Patienten bewusst. Ihnen sind aber nicht unbedingt die zugrunde liegenden Motive klar, die eine angestrebte Übernahme der Krankenrolle und ein Krankheitsverhalten mit hohem selbstinduziertem und iatrogenem Schädigungsrisiko bestimmen. Die Diagnose artifizieller Störungen ist konzeptuell und klassifikatorisch umstritten. Sowohl eine kategoriale Abgrenzung von als auch ein klinisches Kontinuum zwischen somatoformen/dissoziativen Störungen und Simulation werden diskutiert. Die Häufigkeit artifizieller Störungen ist epidemiologisch schwierig zu bestimmen; von einer hohen Dunkelziffer muss ausgegangen werden. In der Ätiopathogenese spielen zumindest bei einer Subgruppe von Patienten frühe traumatisierende Erfahrungen eine wichtige Rolle. Der Verlauf ist durch eine hohe Chronizität ausgezeichnet. Es finden sich aber auch episodische Verlaufsvarianten.



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Mitteilungen der DGN



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Thanks




Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Heavy mite exposure in the environment can induce allergic systemic reactions.

http://alexsfakianakis.blogspot.com/2017/05/mite-hypersensitivity.html

Anaphylaxis

Anaphylaxis is an acute emergency that is potentially fatal and commonly related to an allergic and immunologic trigger requiring immediate effective life-saving treatment [151]. Heavy mite exposure in the environment can induce allergic systemic reactions. More recently, the induction of anaphylaxis through ingestion of mite-contaminated foods has been described [152].

Pancake anaphylaxis, also called oral mite anaphylaxis (OMA), is a relatively new syndrome characterized by severe allergic symptoms occurring immediately after eating foods, especially containing flours, contaminated with mites. These cooked foods contain thermoresistant mite allergens and contaminated wheat flour used to make pancakes is its most common presentation [152]. A variant clinical picture is provoked by physical exercise and is called dust mite ingestion-associated exercise-induced anaphylaxis [153]. OMA is more prevalent in tropical and subtropical areas of the globe where mites grow easily in their warm and humid environments [154]. There are reports in the literature of two fatalities associated with the ingestion of foods contaminated with mites [155, 156]. Mites responsible for OMA include domestic and storage species and can be present in any type of flours. There is an intriguing association of OMA and hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDS) for which there is no good explanation yet and it is more prevalent in patients with house dust mite allergic rhinitis and/or asthma [157]. The higher the contaminated mite ingestion the greater the risk for anaphylaxis. OMA confirmation requires the microscopic documentation and identification of mites in the suspected flour. Alternatively the immunoassay for demonstration of the presence of mite allergens in the suspected flour can be used. It is imperative to try to prevent the worldwide OMA delineating predisposing genetic factors and determining if mite immunotherapy might be efficacious modifying the clinical course of this important variety of food anaphylaxis [152, 158].

Co-sensitization to cockroaches, some crustaceans (shrimp, crab, lobster), shellfish (clams, mussels), and mollusks (snails) is often described and likely due to the presence of allergens in the tropomyosins family, present in some crustaceans (major allergen of shrimp: Pen 1), insects (some flies, mosquitoes, cockroaches), gastropods and mites (Der f 10) [122].

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Prevention of Dust Mite and Dust Mite Allergen Exposure


Justification for Dust Mite Exposure Control

The decision to initiate environmental controls to reduce dust mite exposure can be complex. Total prevention of exposure to mite allergenic material to prevent IgE sensitization to mite allergens in genetically susceptible individuals requires strict, continuous avoidance of mite exposure, which is practically all but impossible [199]. Furthermore, to curtail development of all cross-reacting specific IgE, avoidance of all arthropods would probably be required [200]. The majority of the world's population lives on seacoasts [201] or along rivers [202] and these areas typically have adequate humidity to support growth of dust mites and storage mites during all parts of the year.

Much research has been conducted to determine if it is possible to reduce development of mite-specific IgE-mediated sensitization (primary prevention). Several studies comparing dust mite sensitization rates in children from areas endemically low and areas endemically high in dust mite allergen indicated that the prevalence and degree of sensitization to dust mite was strongly associated with the amount of exposure to mite allergens [203, 204]. A prospective study of mite allergen avoidance in Manchester, UK, [205, 206] using a combination of interventions, decreased Der p 1 from mattresses by 97% to the nanogram range during pregnancy and 12 months after birth in the active group [205]. However, with all possible dust mite exposures at homes of friends and family, on public transportation and in public places and at schools and day care centers, primary prevention of dust mite sensitization by mite allergen avoidance may not be possible [207, 208, 209].

Secondary prevention, or the attempt to reduce the risk of asthma in dust mite sensitized children has also received much attention. The link between asthma and dust mite exposure is one of the most extensively studied relationships between environmental exposure and disease development [210, 211, 212, 213]. In all climates conducive to the growth of dust mites, mite exposure may be one of the factors contributing to the development of asthma [112, 214]. Secondary prevention has also been the goal for many children with allergic rhinitis who are at risk of the subsequent development of asthma. However, to date there is no evidence-based information as to whether mite avoidance may be effective as a secondary preventive measure to prevent/delay asthma development among mite-sensitized individuals, or those with allergic rhinitis.

The relation of dust mite allergen exposure and the worsening of allergic respiratory symptoms is well documented [215]. In one study of 311 subjects both sensitized and exposed to high levels of indoor allergen including dust mite allergen there was significantly lower FEV1% predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6%-10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD20 GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P < .001) as compared with subjects not sensitized and exposed [216]. Adults in a 4-year study who were both sensitized and exposed to high levels of dust mite allergens had increased bronchial hyper-responsiveness [217]. Many additional links between dust mite exposure and allergic disease are documented in the recent environmental practice parameter on dust mites [198]. A reduction in the symptoms experienced by those with atopic dermatitis has also been linked to house dust-mite allergen avoidance [218].

Facilitative factors and Allergen Reservoirs

Controlling factors that facilitate the growth and reproduction of dust mites has been an often sought goal in exposure control. The dependence of dust mites on the water content of the air has been extensively documented [219, 220]. Arid climates have an intrinsically low abundance of dust mites, and the most effective method of controlling dust mite exposure is to live in a very dry climate such as the high desert of New Mexico in the US or the Altiplano or Bolivian Plateau, in west-central South America [202]. Since this is not a practical solution, mimicking these conditions in the home environment as much as possible provides an opportunity to control mite population growth.

Humidity control should be the mainstay of any mite control efforts. The most important factor facilitating dust mite growth, reproduction and allergen production is the availability of water in the surrounding environment [220]. Mites absorb moisture directly from their surroundings under conditions of high moisture and lose water when moisture is low. The mite moisture equilibrium therefore is not directly relative humidity dependent. It is instead dependent of the moisture situation of the local microenvironment and the moisture retention ability of the mite's immediate surroundings such as carpet dust reservoirs or bedding. A simple measurement of relative humidity may not assure an environment free of dust mite activity. Microenvironments that exist in bedding, in carpet next to concrete or in pet lounging areas may provide adequate moisture for mite survival in climates not expected to have a mite presence. A mite surrounded by a hygroscopic microenvironment as moist bedding can survive much dryer conditions than would be expected. Of note, exposure to a moisture rich environment for only a short period can provide enough moisture for growth and metabolism [221].

Although directly linked to water content of the air in the calculation of relative humidity, temperature is also a factor in dust mite survival. Conditions at the extreme ends of the temperature spectrum, either to cold or to hot can impact mite survival although elevated temperature conditions tend to be more lethal than freezing. Mites and their eggs survive poorly when exposed to hot water and clothes dryers but survive during short periods of freezing conditions. The exposure to direct sunlight is an often forgotten factor in the destruction of dust mites [222].

It is not enough to address mite factors facilitating mite population growth. Reservoirs of mite allergen must also be eliminated. House dust mites can be found in any area of the home, however they are most often associated with certain indoor environments including the bedroom carpet, mattresses and bedding, frequently occupied upholstered furniture and in pet lounging areas [223, 224]. Recent investigations have questioned the traditional concepts of the location of dust mite reservoirs indicating that significant exposure can occur in public transportation conveyances and associated with work environments as well as clothing [207].

Climate Factors

Although residents of cold and arid climates are less likely to be exposed to house dust mites, the large majority of the world population is exposed to house dust mites. Nearly half of the people in the world live within 200 km of the coast where humidity levels are typically higher. The rate of population growth in coastal areas is accelerating. In China alone over 400 million live in coastal cities. Dust mite exposures and the allergic problems related to those exposures are likely to increase [201].

Although many climates are naturally conducive to mite growth and allergen production, the artificial control of indoor climates is increasing. Even though it is energy intensive, the use of forced air heating and air conditioning is growing around the world and especially in more affluent economies. Dust mite allergen exposure control is therefore a viable option for large numbers of persons. In many areas seasonal heating requirements result in very dry indoor environments and subsequently dust mite exposure is a seasonal phenomenon. Low humidity conditions can also be obtained through use of air conditioning and dehumidification. Yet, in many areas of the world ambient humidity levels are high enough that producing low humidity levels sufficient to preclude dust mite growth is not practically achievable. The recent Cochrane study on dehumidification alone indicates that evidence of clinical benefits of dehumidification using mechanical ventilation with dehumidifiers is scanty [225]. Indeed, the meta-analysis of multiple dust mite control studies would lead the reader to believe that there is nothing that can be physically done to control dust mites and improve health. Yet, this conclusion is disputed by many experts in the field of allergy [226]. Furthermore, the nature of single source exposure control studies may preclude successful clinical improvement because allergen sensitization is typically to multiple agents.

A significant amount of work has been done on removal of mites and mite allergens through cleaning. It goes without saying that efforts to control mite infestations of the skin and remove mite infestations from clothing are essential in the maintenance of overall health [227]. Humans have been living with dust mites for generations and they might even be described as among our "old friends" [228]. But no physician would advocate for wearing mite infested clothing or sleeping in mite infested bedding. Mite sensitization is likely to occur in genetically susceptible individuals, therefore efforts to reduce instances of elevated mite exposure and thus reduce allergic symptoms are only prudent [229].

Since mite allergens are located in known areas of a typical house [229, 230] removing mite allergen reservoirs is a very effective way to reduce mite allergen exposure. Efforts to remove carpets, drapes, upholstered furniture and any other fabric covered objects from the living environment can effectively reduce mite allergen exposure. The extent to which these items are removed will ultimately be a matter of personal preference. Since mite allergens are known to be heavy and not aerodynamically suited for airborne disbursal [34] and high humidity microenvironments are known to exist in bedding it is logical to focus dust mite reduction efforts on bedding. Efforts to enclose mattresses, box springs and pillows in mite-impermeable covers are known to be very effective [231]. However, it is important to mention that the efficacy of allergen avoidance in patients with already established rhinitis or asthma is a matter of debate [232, 233, 234, 235].

Washing bedding in hot water and even with bleach and drying bedding in very hot conditions or even in direct sunlight are known to reduce both the presence of mite allergen and the mites themselves [236, 237]. Washing bedding and clothing removes mite allergens and kills mites. Most of the killing is through drowning, although washing in hotter water kills more mites. The temperature used to wash bedding has become an issue. Elevated temperatures are more energy intensive and hotter water is a scalding hazard. Experts agree that washing is better than not washing and washing with water that is 48° Celsius provides optimum mite killing and home safety [199].

Heat treatment can be effective in killing mites and their eggs. Treatment of cloth at 95° Celsius killed all mites present [238]. However, treatment at 40 °C under dry and wet conditions allowed approximately 80% of all mite eggs to survive. Under dry heat at 50 °C, the thermal death point of dust mite eggs occurred at 5 h and at 60 °C death occurred almost instantaneously [239]. Presumably the eggs survive heat better than the mites themselves. Homes treated with heat-steam over a period of months showed a sustained reduction of Der p 1 and Der p 2 compared to sham treated homes [240] However, mite allergens have been demonstrated to be stable even at elevated temperatures [241].

Although the practice has fallen into senescence in the modern world of appliances, there was a time when frequently placing bedding in direct sunlight for several hours was practiced in many cultures. It has been demonstrated that ultraviolet irradiation is lethal to many organisms including dust mites [242, 243].

Many harsh chemicals are known to kill dust mites or denature mite allergens in industrial and household settings. Agents like tannic acid, Benzyl benzoate, Disodium octaborate tetrahydrate, tri-n-butyl tin maleate, pirimiphos methyl and even "essential oils" like methyl eugenol have been described in the literature to effectively kill mites [244, 245, 246, 247, 248]. However, they are all dangerous at some concentration and cannot be recommended for use by patients or homeowners [199].

It has been suggested that freezing can be effective in killing dust mites and the recommendation to place small cloth items like stuffed animals in the freezer compartment of house hold refrigerators has been frequently given out by allergists. However, there is little evidence that this is effective. There may be some mite death due to desiccation in the dry environment of a household freezer. But, dust mite eggs have been shown to resist freezing at temperatures above −70° Celsius [222]. And, freezing is not effective in removing dust mite allergen from reservoirs because dust mite allergen is stable at low temperatures for extended periods of time [239].

Air conditioning would have a twofold impact on dust mite populations. The cool temperatures will slow mite metabolism and reproduction and reduce moisture need for mite survival. Microenvironments or increased humidity can be reduced using a dehumidifier and/or air conditioning. The absence of air conditioning has been shown to be a factor contributing to increased mite allergen levels in US homes [249]. Air conditioners must be operated for a long time to remove sufficient moisture from the air to effectively decrease room humidity. Mechanical ventilation heat pump recovery units in the UK failed to achieve the desired mite reduction results [250].

Evidence on clinical benefits of dehumidification using mechanical ventilation with dehumidifiers remains scanty [225]. Although dehumidification and air conditioning doubtlessly reduce overall dust mite exposure [251], the difficulty in using dehumidification alone in damp environments to decrease dust mite antigen exposure has been described in a recent Cochrane review [225].

Summary of current recommendations

Most publications on allergy and dust mite control would agree that a comprehensive program of personal hygiene, bed hygiene, properly fitted allergen-impermeable covers, cleaning, dehumidification or air conditioning and appropriate food storage in very damp climates can reduce exposure to house dust mite allergens. It is a stretch further to conclude that the above steps can improve symptoms in those already allergic to dust mites. However, depending on the sensitivity and life style of the allergic person, prudent efforts over an extended period of time are likely to result in gradual improvement in health. The fact that current studies do not provide sufficient evidence for critical reviews to conclude there is unequivocal benefit is no reason to abandon logical and prudent efforts to reduce mite exposure.


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Mite Allergy Research The authors view the following as currently unmet needs in mite allergy research: Since mites constitute the most important allergen source worldwide the information contained in this document needs to be disseminated to all ranks of the medical establishment for educational purposes and to stimulate research Increased knowledge on the cellular basis of the immune responses to mites A better understanding of the link between mite sensitization and allergic diseases Better insights into the genetic influences controlling IgE responses to mite allergens. Effects of epigenetic factors Improved mite allergen standardization Development of purified mite allergens with defined clinically relevant epitopes for molecular diagnosis and evaluation of the response to immunotherapy Development of objective methods to assess allergen exposure and environmental control outcomes Better strategies for immunotherapy and immunoprophylaxis of mite allergy: recombinant allergens, h

http://alexsfakianakis.blogspot.com/2017/05/mite-hypersensitivity.html
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Rick factors for medical and allergic events during air travel An increase of passenger’s age Flight stress and anxiety, including increased security procedures Disruption of routine Changes in the cabin environment (temperature, humidity, air pressure) Decreased seat space Flight delays Alcohol/drug intake Longer flights Altered circadian rhythm Jet lag Pre-existing medical conditions

http://alexsfakianakis.blogspot.com/2017/05/in-flight-allergic-emergencies.html
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

In-flight treatment of allergic emergencies and asthma Treating medical emergencies during flight is a major challenge and air travel is an important concern for subjects with asthma and a history of a SAR. The resources to treat allergic emergencies are somewhat limited. In the United States, the Federal Aviation Administration requires the inclusion of epinephrine in medical kits carried on board [18]. These emergency medical kits typically contain the following medications [19]: Aqueous epinephrine (adrenaline) 1:10000 and 1:1000 dilution. Albuterol (salbutamol) for nebulization. Bronchodilator aerosol inhaler. Cortisol (hydrocortisone). Antihistamines tablets and injectable (commonly diphenhydramine). A recommendation from this World Allergy Organization (WAO) expert group for in-flight treatment of a SAR and AE is: a) For AE, inhaled bronchodilator and oxygen. Consider an oral, intramuscular or intravenous corticosteroid for moderate to severe symptoms and intramuscular epinephr

http://alexsfakianakis.blogspot.com/2017/05/in-flight-allergic-emergencies.html
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Measures that reduce the risk of an in-flight reaction to peanut and tree nuts 1. Passengers requesting any kind of special accommodation (e.g., peanut/tree nut snacks not be distributed, announcement to not eat items with peanut/tree nut, request special peanut/tree nut-free meal, buffer zone, pre-board, request to sit in a certain seat/zone). 2. Peanut/tree nut-free meals. 3. Wiping of tray tables 4. Avoidance of airline pillows or blankets 5. Buffer zones around which peanut or nut products cannot be consumed 6. Request other passengers not to consume peanut/tree nut-containing products 7. Announcement that passengers do not eat peanut/tree nut containing goods 8. Not consuming airline-provided food

http://alexsfakianakis.blogspot.com/2017/05/in-flight-allergic-emergencies.html
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Recommendations to prevent and manage in-flight allergic events • Promote the prevention of allergic diseases via passenger education • Medical consultation for high-risk passengers before traveling • Train and re-train aircrews • Promote general preventive measures during the flight: hydration, food allergen avoidance (especially peanuts, tree nuts, other foods, as necessary) • Provide an appropriate place for furry pets away from subjects with pet allergy • Provide for sufficient quantities of appropriate medications: epinephrine (adrenaline), β2 agonists for inhalation and nebulization, oral and injectable corticosteroids and antihistamines • Oxygen




Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Are medical outliers associated with worse patient outcomes? A retrospective study within a regional NHS hospital using routine data

Objective

To explore the quality and safety of patients’ healthcare provision by identifying whether being a medical outlier is associated with worse patient outcomes. A medical outlier is a hospital inpatient who is classified as a medical patient for an episode within a spell of care and has at least one non-medical ward placement within that spell.

Data sources

Secondary data from the Patient Administration System of a district general hospital were provided for the financial years 2013/2014–2015/2016. The data included 71 038 medical patient spells for the 3-year period.

Study design

This research was based on a retrospective, cross-sectional observational study design. Multivariate logistic regression and zero-truncated negative binomial regression were used to explore patient outcomes (in-hospital mortality, 30-day mortality, readmissions and length of stay (LOS)) while adjusting for several confounding factors.

Principal findings

Univariate analysis indicated that an outlying medical in-hospital patient has higher odds for readmission, double the odds of staying longer in the hospital but no significant difference in the odds of in-hospital and 30-day mortality. Multivariable analysis indicates that being a medical outlier does not affect mortality outcomes or readmission, but it does prolong LOS in the hospital.

Conclusions

After adjusting for other factors, medical outliers are associated with an increased LOS while mortality or readmissions are not worse than patients treated in appropriate specialty wards. This is in line with existing but limited literature that such patients experience worse patient outcomes. Hospitals may need to revisit their policies regarding outlying patients as increased LOS is associated with an increased likelihood of harm events, worse quality of care and increased healthcare costs.



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Screening for coronary artery disease in patients with type 2 diabetes: a meta-analysis and trial sequential analysis

Objective

To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings.

Methods

Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included. Data were summarised with Mantel-Haenszel relative risk. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac events (non-fatal myocardial infarction and cardiovascular death); secondary outcomes were non-fatal myocardial infarction, myocardial revascularisations and heart failure.

Results

One hundred thirty-five references were identified and 5 studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all-cause deaths and 100 cardiac events. Screening for coronary artery disease was not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to 1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility boundaries were reached for all-cause mortality and a relative risk reduction of 40% between treatments could be discarded. However, there is not enough information for firm conclusions for cardiac events. For secondary outcomes no benefit or harm was identified; optimal sample sizes were not reached.

Conclusion

Current available data do not support screening for coronary artery disease in patients with type 2 diabetes for preventing fatal events. Further studies are needed to assess the effects on cardiac events.

PROSPERO

CRD42015026627.



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Multimorbidity as an important issue among women: results of a gender difference investigation in a large population-based cross-sectional study in West Asia

Objectives

To investigate the impact of gender on multimorbidity in northern Iran.

Design

A cross-sectional analysis of the Golestan cohort data.

Setting

Golestan Province, Iran.

Study population

49 946 residents (age 40–75 years) of Golestan Province, Iran.

Main outcome measures

Researchers collected data related to multimorbidity, defined as co-existence of two or more chronic diseases in an individual, at the beginning of a representative cohort study which recruited its participants from 2004 to 2008. The researchers utilised simple and multiple Poisson regression models with robust variances to examine the simultaneous effects of multiple factors.

Results

Women had a 25.0% prevalence of multimorbidity, whereas men had a 13.4% prevalence (p<0.001). Women of all age-groups had a higher prevalence of multimorbidity. Of note, multimorbidity began at a lower age (40–49 years) in women (17.3%) compared with men (8.6%) of the same age (p<0.001). This study identified significant interactions between gender as well as socioeconomic status, ethnicity, physical activity, marital status, education level and smoking (p<0.01).

Conclusion

Prevention and control of multimorbidity requires health promotion programmes to increase public awareness about the modifiable risk factors, particularly among women.



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Validity and reliability of the Patient Centred Assessment Method for patient complexity and relationship with hospital length of stay: a prospective cohort study

Objectives

Several instruments for evaluating patient complexity have been developed from a biopsychosocial perspective. Although relationships between the results obtained by these instruments and the length of stay in hospital have been examined, many instruments are complicated and not easy to use. The Patient Centred Assessment Method (PCAM) is a candidate for practical use. This study aimed to test the validity and reliability of the PCAM and examine the correlations between length of hospital stay and PCAM scores in a regional secondary care hospital in Japan.

Design

Prospective cohort study.

Participants and setting

Two hundred and one patients admitted to Ouji Coop Hospital between July 2014 and September 2014.

Main predictor

PCAM total score in initial phase of hospital admission.

Main outcome

Length of stay in hospital.

Results

Among 201 patients (Female/Male=98/103) with mean (SD) age of 77.4±11.9 years, the mean PCAM score was 25±7.3 and mean (SD) length of stay in hospital (LOS) 34.1±40.9 days. Using exploratory factor analysis to examine construct validity, PCAM evidently has a two-factor structure, comprising medicine-oriented and patient-oriented complexity. The Spearman rank correlation coefficient for evaluating criterion-based validity between PCAM and INTERMED was 0.90. For reliability, Cronbach’s alpha was 0.85. According to negative binomial regression analyses, PCAM scores are a statistically significant predictor (p<0.001) of LOS after adjusting for age, gender, Mini Nutritional Assessment Short-Form, Charlson Comorbidity Index, serum sodium concentration, total number of medications and whether public assistance was required. In another model, each factor in PCAM was independently correlated with length of stay in hospital after adjustment (medicine-oriented complexity: p=0.001, patient-oriented complexity: p=0.014).

Conclusion

PCAM is a reliable and valid measurement of patient complexity and PCAM scores have a significant correlation with hospital length of stay.



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Selective impact of disease on short-term and long-term components of self-reported memory: a population-based HUNT study

Background

Subjective memory is commonly considered to be a unidimensional measure. However, theories of performance-based memory suggest that subjective memory could be divided into more than one dimension.

Objective

To divide subjective memory into theoretically related components of memory and explore the relationship to disease.

Methods

In this study, various aspects of self-reported memory were studied with respect to demographics and diseases in the third wave of the HUNT epidemiological study in middle Norway. The study included all individuals 55 years of age or older, who responded to a nine-item questionnaire on subjective memory and questionnaires on health (n=18 633).

Results

A principle component analysis of the memory items resulted in two memory components; the criterion used was an eigenvalue above 1, which accounted for 54% of the total variance. The components were interpreted as long-term memory (LTM; the first component; 43% of the total variance) and short-term memory (STM; the second component; 11% of the total variance). Memory impairment was significantly related to all diseases (except Bechterew’s disease), most strongly to brain infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary disease and whiplash. For most diseases, the STM component was more affected than the LTM component; however, in cancer, the opposite pattern was seen.

Conclusions

Subjective memory impairment as measured in HUNT contained two components, which were differentially associated with diseases.



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Four-year nationwide incidence of retinitis pigmentosa in South Korea: a population-based retrospective study from 2011 to 2014

Objective

To determine the incidence of retinitis pigmentosa (RP) in South Korea.

Design

Nationwide, population-based retrospective study.

Setting

Census population of South Korea

Participants

This study involved the entire population of South Korea (n=47 990 761). Patients confirmed as having RP by an ophthalmologist from 1 January 2011 to 31 December 2014 were included.

Primary outcome measure

The average incidence of RP during the 4-year study period was estimated using population data from the 2010 Korean census.

Results

A total of 3144 (1567 men and 1577 women) patients confirmed as having RP were identified. The average incidence of RP was 1.64 cases/100 000 person-years (95% CI 1.58 to 1.70). The incidence of RP distribution skewed to the left across age groups, with one smaller peak observed in the 20–24-year-old age group (1.24 cases/100 000 person-years) and a larger peak observed in the 65–69-year-old age group (3.26 cases/100 000 person-years). The overall incidence was similar in men and women (1.64 cases/100 000 person-years (95% CI 1.56 to 1.73) for men; 1.63 cases/100 000 person-years (95% CI 1.55 to 1.72) for women).

Conclusions

Our study’s estimates of the nationwide population-based incidence of RP in an Asian population will help advance the understanding of the disease onset and allow healthcare systems to plan accordingly.



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Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: a systematic review and dose-response meta-analysis

Objectives

To examine the association between coffee, including caffeinated and decaffeinated coffee, with hepatocellular carcinoma (HCC) and assess the influence of HCC aetiology and pre-existing liver disease.

Design

We performed a systematic review and meta-analysis. We calculated relative risks (RRs) of HCC according to caffeinated and decaffeinated coffee consumption using a random-effects dose–response meta-analysis. We tested for modification of the effect estimate by HCC aetiology and pre-existing liver disease. We judged the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

Results

We found 18 cohorts, involving 2 272 642 participants and 2905 cases, and 8 case–control studies, involving 1825 cases and 4652 controls. An extra two cups per day of coffee was associated with a 35% reduction in the risk of HCC (RR 0.65, 95% CI 0.59 to 0.72). The inverse association was weaker for cohorts (RR 0.71, 95% CI 0.65 to 0.77), which were generally of higher quality than case–control studies (RR 0.53, 95% CI 0.41 to 0.69). There was evidence that the association was not significantly altered by stage of liver disease or the presence/absence of high alcohol consumption, high body mass index, type 2 diabetes mellitus, smoking, or hepatitis B and C viruses. An extra two cups of caffeinated and decaffeinated coffee (2 and 3 cohort studies, respectively) were associated with reductions of 27% (RR 0.73, 95% CI 0.63 to 0.85) and 14% (RR 0.86, 95% CI 0.74 to 1.00) in the risk of HCC. However, due to a lack of randomised controlled trials, potential publication bias and there being no accepted definition of coffee, the quality of evidence under the GRADE criteria was ‘very low’.

Conclusions

Increased consumption of caffeinated coffee and, to a lesser extent, decaffeinated coffee are associated with reduced risk of HCC, including in pre-existing liver disease. These findings are important given the increasing incidence of HCC globally and its poor prognosis.



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Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study)

Introduction

In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required. Therefore, we aim to determine the effects of treatment with SGLT-2 inhibitors or metformin for reducing visceral fat in 106 Asian patients with type 2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50 mg daily) for poor glycaemic control.

Methods and analysis

A prospective, multicentre, blinded-endpoint phase IV randomised controlled study will be conducted to evaluate the safety and efficacy of a 24-week treatment with either an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg daily) or metformin (1000 mg daily). The primary outcome is the rate of change in the total area of visceral fat for patients in both treatment groups, measured using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical information, will perform centralised analysis of the images in a unified measurement condition.

Ethics and dissemination

The protocol was approved by the institutional review board of each hospital. This study is ongoing and due to finish in April 2017. The findings of this study will be disseminated via peer-reviewed publications and conference presentations, and will also be disseminated to participants.

Trial registration number

UMIN000015170, R000016861 (http://ift.tt/2pikn17); Pre-results



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Using a patient decision aid for insulin initiation in patients with type 2 diabetes: a qualitative analysis of doctor-patient conversations in primary care consultations in Malaysia

Objective

To investigate whether the use of apatient decision aid (PDA) for insulin initiation fulfils its purpose of facilitating patient-centred decision-making through identifying how doctors and patients interact when using the PDA during primary care consultations.

Design

Conversation analysis of seven single cases of audio-recorded/video-recorded consultations between doctors and patients with type 2 diabetes, using a PDA on starting insulin.

Setting

Primary care in three healthcare settings: (1) one private clinic; (2) two public community clinics and (3) one primary care clinic in a public university hospital, in Negeri Sembilan and the Klang Valley in Malaysia.

Participants

Clinicians and seven patients with type 2 diabetes to whom insulin had been recommended. Purposive sampling was used to select a sample high in variance across healthcare settings, participant demographics and perspectives on insulin.

Primary outcome measures

Interaction between doctors and patients in a clinical consultation involving the use of a PDA about starting insulin.

Results

Doctors brought the PDA into the conversation mainly by asking information-focused ‘yes/no’ questions, and used the PDA for information exchange only if patients said they had not read it. While their contributions were limited by doctors’ questions, some patients disclosed issues or concerns. Although doctors’ PDA-related questions acted as a presequence to deliberation on starting insulin, their interactional practices raised questions on whether patients were informed and their preferences prioritised.

Conclusions

Interactional practices can hinder effective PDA implementation, with habits from ordinary conversation potentially influencing doctors’ practices and complicating their implementation of patient-centred decision-making. Effective interaction should therefore be emphasised in the design and delivery of PDAs and in training clinicians to use them.



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Health status and needs of cancer survivors attending the Sydney Survivorship Centre clinics and programmes: a protocol for longitudinal evaluation of the centres services

Introduction

The care of cancer survivors after primary adjuvant treatment is recognised as a distinct phase of the cancer journey. Recent research highlights the importance of lifestyle factors in treating symptoms, potentially decreasing risk of a cancer recurrence and modifying the risk of developing other chronic illnesses that are increased in the cancer population. Survivorship services aim to deliver care that addresses these issues. The overall aims are to determine the health status of cancer survivors and to evaluate the services offered by the Sydney Survivorship Centre (SSC).

Methods and analysis

This is an observational single-centre study evaluating the longitudinal physical and psychological health, symptoms, quality of life and lifestyle (physical activity and nutrition) of early stage cancer survivors attending the multidisciplinary Sydney Survivorship Clinic and survivors (at any stage of the cancer journey) and caregivers participating in SSC courses. Evaluation of patient satisfaction is included. Patient-reported outcomes and patient characteristics will be summarised using descriptive statistics with Spearman rank sum correlation coefficients to determine associations between patient-reported outcomes. Regression modelling may be used to further evaluate associations and to investigate risk factors and predictors of health outcomes. Qualitative data will be analysed using thematic analysis to identify themes. Sample size will be determined by attendance of consenting patients at clinics and courses.

Ethics and dissemination

The study has received ethics approval from the Concord Repatriation General Hospital Human Research Ethics Committee (HREC/14/CRGH/23). The results will be published and presented at appropriate conferences.

This study will provide important information regarding the health status and needs of Australian cancer survivors and the ability of the survivorship centre to address these needs. These data will shape the future direction of survivorship care in Australia and facilitate the design of interventions or measures to provide better quality of care to this patient population.



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Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough

Objective

To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing.

Design

Primary care feasibility cluster randomised controlled trial.

Setting

32 general practices in South West England recruiting children from October 2014 to April 2015.

Participants

Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI).

Intervention

A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record.

Controls

Usual practice, with clinicians recording data on symptoms, signs and treatment decisions.

Results

Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children’s RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm.

Conclusion

Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records.

Trial registration number

ISRCTN 23547970

UKCRN study ID

16891



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Nursing home team-care deprescribing study: a stepped-wedge randomised controlled trial protocol

Introduction

An ageing population has become an urgent concern for Asia in recent times. In nursing homes, polypharmacy has also become a compounding issue. Deprescribing practice is an evidence-based strategy to provide a better outcome in this group of patients; however, its implementation in nursing homes is often challenging, and prospective outcome data on deprescribing practice in the elderly is lacking. Our study assesses the implementation of team-care deprescribing to understand the benefits of this practice in geriatric setting and to explore the factors affecting deprescribing practice.

Methods and analysis

This multicentre prospective study consists of a prestudy interview questionnaire, and a preintervention and postintervention study to be conducted in the nursing home setting on residents at least 65 years old and on five or more medications. We will employ a cluster randomised stepped-wedge interventional design, based on a five-step (reviewing, checking, discussion, communication and documentation) team-care deprescribing practice coupled with the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well as drug interaction checking), to assess the health and pharmacoeconomic outcome in nursing homes’ practice. Primary outcome measures of the intervention will consist of fall risks using a fall risk assessment tool. Other outcomes assessed include fall rates, pill burden including number of pills per day, number of doses per day and number of medications prescribed. Cost-related measures will include the use of cost–benefit analysis, which is calculated from the medication cost savings from deprescribing. For the prestudy interview questionnaire, findings will be analysed qualitatively using thematic analysis.

Ethics and dissemination

This study is approved by the Domain Specific Review Board of National Healthcare Group, Singapore (2016/00422) and Monash University Human Research Ethics Committee (2016-1430-7791). The study findings shall be disseminated in international conferences and peer-reviewed publications. The study is registered with ClinicalTrials.gov (NCT02863341), Pre-results



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Telehealthcare for patients suffering from chronic obstructive pulmonary disease: effects on health-related quality of life: results from the Danish 'TeleCare North cluster-randomised trial

Objective

To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).

Design

A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).

Setting

Twenty-six municipal districts in the North Denmark Region of Denmark.

Participants

Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.

Main outcome measures

Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2. Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.

Results

In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was –2.6 (SD 12.4) in the telehealthcare group and –2.8 (SD 11.9) in the usual practice group. The raw mean difference in MCS scores in the same period was –4.7 (SD 16.5) and –5.3 (SD 15.5) for telehealthcare and usual practice, respectively. The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI –1.4 to 1.7) and 0.4 (95% CI –1.7 to 2.4), respectively.

Conclusions

The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.

Trial registration number

NCT01984840; Results.



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Autism spectrum disorder: updated prevalence and comparison of two birth cohorts in a nationally representative Australian sample

Objectives

This study aimed to (1) provide an update on the prevalence of parent-reported autism spectrum disorder (ASD) diagnosis and new information about teacher-reported ASD in two nationally representative Australian cohorts at ages 10–11 years, (2) examine differences in cohort demographic and clinical profiles and (3) compare the prevalence of teacher-reported ASD and any changes in categorisation over time across the cohorts.

Design

Secondary analyses were undertaken using data from the Longitudinal Study of Australian Children (LSAC).

Participants

Children were recruited at kindergarten age (K cohort; birth year 1999/2000) and birth (B cohort; birth year 2003/2004), with follow-up of every 2 years for six waves.

Primary outcome measures

Parent-reported and teacher-reported ASD diagnosis was ascertained at three time points (waves 4–6).

Results

At age 10–11 years, the adjusted prevalence of parent-reported ASD diagnosis was 3.9% (95% CI 3.2 to 4.5) and 2.4% (95% CI 1.6 to 2.9) in the B and K cohorts, respectively. Teacher-reported prevalence of ASD was 1.7% (95% CI 1.2 to 2.1) in the B cohort and 0.9% (95% CI 0.56 to 1.14) in the K cohort. Parents reported fewer conduct and peer problems and teachers more pro-social behaviour in B relative to K cohort ASD children. Children reported only by parents in the later-born B cohort had milder behaviour problems than parent-agreed and teacher-agreed cases. Although individual switching to ASD from other categories from 8–9 to 10–11 years was low (K cohort n=5, B cohort n=6), teachers reported more children with ASD in the B than K cohort at 10–11 years and fewer children with emotional/ behavioural problems.

Conclusions

The higher prevalence of parent-reported and teacher-reported ASD diagnosis in the later-born cohort may be partially explained by identifying children with milder behavioural problems as ASD and a change in the use of diagnostic categories in schools.



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Maternal alcohol disorders and school achievement: a population cohort record linkage study in Western Australia

Objective

Maternal alcohol use disorder is a risk factor for a range of developmental outcomes in children. This study examines school achievement in children of Indigenous and non-Indigenous mothers with an alcohol-related diagnosis.

Design, setting and participants

This is a Western Australian population cohort study of mothers with a record of an alcohol-related diagnosis classified by the International Classification of Diseases Revisions 9/10 codes as recorded on administrative databases, and of their offspring born between 1989 and 2007 (n=18 486 exposed children), with a frequency matched comparison cohort of mothers with no record of alcohol diagnosis and their offspring (n=48 262 comparison children).

Outcomes

Records were linked with school achievement data for numeracy and literacy from Years 3, 5, 7 and 9 (age range: ~8–14 years) based on statewide and national testing. Mixed multivariate models with a random intercept per child were used to assess the relationship between exposure and the timing of exposure with failure to meet minimum standardised benchmarks.

Results

Academic achievement was lower in all testing domains (reading, writing, spelling and numeracy) among children of mothers with an alcohol diagnosis and persisted across all year groups examined. The highest ORs at Year 9 for non-Indigenous children were in reading (adjusted OR (aOR) 1.6, 95% CI 1.4 to 1.8) and in writing for Indigenous children (aOR 2.0, 95% CI 1.8 to 2.3).

Conclusion

Children of mothers with alcohol use disorders are at risk of not meeting minimum educational benchmarks in numeracy and literacy, with the risk highest among Indigenous children.



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Possible relationship between general and pregnancy-related anxiety during the first half of pregnancy and the birth process: a prospective cohort study

Objectives

The rate of interventions during childbirth has increased dramatically during the last decades. Maternal anxiety might play a role in the progress of the labour process and interventions during labour. This study aimed to identify associations between anxiety in the first half of pregnancy and the birth process, including any interventions required during labour. In addition, differences in the associations by parity and ethnicity were explored.

Design

Prospective cohort study.

Setting

Primary care midwifery practices and secondary/tertiary care obstetric practices in Amsterdam, participating in the multiethnic ABCD (Amsterdam Born Children and their Development) study (participation rate 96%; response 8266/12 373 (67%)).

Participants

Included were women with singletons, alive at labour start, with a gestational age ≥24 weeks (n=6443).

Independent variable

General anxiety (State-Trait Anxiety Inventory state) and pregnancy-related anxiety (Pregnancy-Related Anxieties Questionnaire (PRAQ)) were self-reported in the first half of pregnancy.

Outcomes

Associations between both forms of anxiety and several indicators of the birth process were analysed. Subgroup analyses were performed for parity and ethnicity.

Results

The prevalence of high general anxiety (State-Trait Anxiety Inventory score ≥43) and pregnancy-related anxiety (PRAQ score ≥P90) were 30.9% and 11.0%, respectively. After adjustment, in nulliparae, both general anxiety and pregnancy-related anxiety were associated with pain relief and/or sedation (OR for general anxiety 1.23; 95% CI 1.02 to 1.48; OR for pregnancy-related anxiety 1.45; 95% CI 1.14 to 1.85). In multiparae, general anxiety was associated with induction of labour (OR 1.53; 95% CI 1.16 to 2.03) and pregnancy-related anxiety was associated with primary caesarean section (OR 1.66; 95% CI 1.02 to 2.70). Associations were largely similar for all ethnicities.

Conclusions

High levels of general and pregnancy-related anxiety in early pregnancy contribute modestly to more interventions during the birth process with similar associations between ethnic groups, but with some differences between nulliparae and multiparae.



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The effect of empagliflozin on oxidative nucleic acid modifications in patients with type 2 diabetes: protocol for a randomised, double-blinded, placebo-controlled trial

Introduction

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D). Although glycaemic control reduces microvascular complications, the effect of intensive treatment strategies or individual drugs on macrovascular diseases is still debated. RNA oxidation is associated with increased mortality in patients with T2D. Inspired by animal studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor (empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin that demonstrated improved cardiovascular outcomes in patients with T2D at high risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative stress.

Methods and analysis

In this randomised, double-blinded and placebo-controlled study, 34 adult males with T2D will be randomised (1:1) to empagliflozin or placebo once daily for 14 days as add-on to ongoing therapy. The primary endpoints will be changes in 24-hour urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) determined before and after intervention (by ultra-performance liquid chromatography tandem mass-spectrometry). Additionally, fasting levels of malondialdehyde (MDA) will be determined in plasma before and after intervention (by high-performance liquid chromatography). Further, the plasma levels of iron, transferrin, transferrin-saturation, and ferritin are determined to correlate the iron metabolism to the markers of oxidative modifications.

Ethics and dissemination

The study protocol has been approved by the Regional Committee on Biomedical Research Ethics (approval number H-16017433), the Danish Medicines Agency, and the Danish Data Protection Agency, and will be carried out under the surveillance and guidance of the GCP unit at Bispebjerg Frederiksberg Hospital, University of Copenhagen in compliance with the ICH-GCP guidelines and in accordance with the Declaration of Helsinki. The results of this study will be presented at national and international conferences, and submitted to a peer-reviewed international journal with authorship in accordance with Internation Committee of Medical Journal Editors (ICMJE) Recommendations state.

Trial registration

Study name: EMPOX; Pre-results: clinicaltrials.gov (NCT02890745). Protocol version 5.1 - August, 2016.



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A retrospective cohort study of the utility of the modified early warning score for interfacility transfer of patients with traumatic injury

Objective

The modified early warning score (MEWS) is a ‘track and trigger’ score using routine physiological vital signs. The objective is to determine if the pretransfer MEWS can be used for predicting outcomes in trauma patients requiring interfacility transfer to higher levels of care.

Design, setting and participants

Retrospective study of consecutively transferred trauma patients into a level-II trauma centre from 2013 to 2014.

Interventions

None.

Outcome measures

Mortality, intensive care unit (ICU) admission, operative procedure, MEWS deterioration in-transit, air transport interfacility, secondary overtriage (low injury severity score (ISS) <10, LOS<1 day, discharged home) and severe injury (ISS ≥16). The association between the pretransfer MEWS and outcomes were analysed with Cochran-Armitage trend tests, receiver operator characteristic (ROC) curves and univariate logistic regression.

Results

There were 587 transferred patients; outcomes were reported in 339 patients with complete data on all five vital signs used to calculate the MEWS. The MEWS ranged from 0 to 9 (median of 1). There was a significant linear relationship between MEWS and study outcomes, especially mortality, ICU admission, air medical transport and severe injury (p<0.001 for all). A threshold score ≥4 was identified by ROC analysis; 11.2% of patients had MEWS ≥4. Outcomes were significantly worse in patients with MEWS ≥4 versus <4: mortality (26.2% vs 3.0%, OR=11.59, p<0.001); ICU admission (73.7% vs 47.2%, OR=3.14, p=0.003); air transfer (42.1% vs 15.6%, OR=3.93, p<0.001) and severe injury (59.5% vs 27.2%, OR=3.9, p<0.001). The MEWS was not associated with surgery, in-transit MEWS deterioration or secondary overtriage.

Conclusion

Pretransfer MEWS ≥4 may be used by the receiving facility for predicting injury severity, mortality, air transport and ICU resource use. In the interfacility transport setting, the MEWS may be useful for identifying patients with less obvious need for transfer or requiring more expeditious transfer.



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Association between serum osmolarity and mortality in patients who are critically ill: a retrospective cohort study

Objectives

This research aims to explore the association between serum osmolarity and mortality in patients who are critically ill with specific categories of disease.

Design

A retrospective cohort study.

Setting and participants

Data were extracted from an online database named ‘Multiparameter Intelligent Monitoring in Intensive Care II’. 16 598 patients were included.

Methods

Patients were divided into six disease subgroups based on the diagnosis at admission: cardiac, cerebral, vascular, gastrointestinal, respiratory and non-respiratory. The association between maximum osmolarity (osmolaritymax) and hospital mortality in each subgroup was evaluated using osmolaritymax as a design variable (six levels).

Results

Analysis of the 16 598 patients revealed a ‘U’-shaped relationship between osmolarity and mortality with a threshold of 300 mmoL/L. For patients with non-respiratory disease, both hypo-osmolarity and hyperosmolaritymax were associated with increased mortality, with the OR increasing from osmolaritymax level 3 (OR: 1.98, 95% CI 1.69 to 2.33, p<0.001) to level 6 (OR: 4.45, 95% CI 3.58 to 5.53, p<0.001), using level 2 (290–309 mmoL/L) as the reference group. For patients with respiratory disease, however, neither hypo-osmolarity nor hyperosmolaritymax was significantly associated with mortality (levels 1 to 5) except for extreme hyperosmolaritymax (≥340 mmoL/L, OR: 2.03, 95% CI 1.20 to 3.42, p=0.007). ORs of mortality in the other four subgroups (cardiac, cerebral, vascular, gastrointestinal) were similar, with OR progressively increasing from level 3 to 6. In all six subgroups, vasopressin use was consistently associated with increased mortality.

Conclusions

Hyperosmolarity is associated with increased mortality in patients who are critically ill with cardiac, cerebral, vascular and gastrointestinal admission diagnoses, with thresholds at 300 mmoL/L. For patients with respiratory disease, however, no significant association was detected.



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Study of Meta-analysis strategies for network inference using information-theoretic approaches

Reverse engineering of gene regulatory networks (GRNs) from gene expression data is a classical challenge in systems biology. Thanks to high-throughput technologies, a massive amount of gene-expression data ha...

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Feature analysis for classification of trace fluorescent labeled protein crystallization images

Large number of features are extracted from protein crystallization trial images to improve the accuracy of classifiers for predicting the presence of crystals or phases of the crystallization process. The exc...

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Multi-class computational evolution: development, benchmark evaluation and application to RNA-Seq biomarker discovery

A computational evolution system (CES) is a knowledge discovery engine that can identify subtle, synergistic relationships in large datasets. Pareto optimization allows CESs to balance accuracy with model comp...

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Discovering feature relevancy and dependency by kernel-guided probabilistic model-building evolution

Discovering relevant features (biomarkers) that discriminate etiologies of a disease is useful to provide biomedical researchers with candidate targets for further laboratory experimentation while saving costs...

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Rapid development of entity-based data models for bioinformatics with persistence object-oriented design and structured interfaces

Databases are imperative for research in bioinformatics and computational biology. Current challenges in database design include data heterogeneity and context-dependent interconnections between data entities....

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Rapid diagnosis of herpes zoster by loop-mediated isothermal amplification in a pregnant woman showing folliculitis-like eruption without vesicles



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Crk adaptor proteins regulate CD3ζ chain phosphorylation and TCR/CD3 down-modulation in activated T cells

Publication date: August 2017
Source:Cellular Signalling, Volume 36
Author(s): Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Yael Babichev, Sigal Gelkop, Noah Isakov
T cell receptor (TCR) recognition of a peptide antigen in the context of MHC molecules initiates positive and negative cascades that regulate T cell activation, proliferation and differentiation, and culminate in the acquisition of effector T cell functions. These processes are a prerequisite for the induction of specific T cell-mediated adaptive immune responses. A key event in the activation of TCR-coupled signaling pathways is the phosphorylation of tyrosine residues within the cytoplasmic tails of the CD3 subunits, predominantly CD3ζ. These transiently formed phosphotyrosyl epitopes serve as docking sites for SH2-domain containing effector molecules, predominantly the ZAP70 protein tyrosine kinase, which is critical for signal propagation. We found that CrkI and CrkII adaptor proteins also interact with CD3ζ in TCR activated-, but not in resting-, T cells. Crk binding to CD3ζ was independent of ZAP70 and also occurred in ZAP70-deficient T cells. Binding was mediated by Crk-SH2 domain interaction with phosphotyrosine-containing motifs on CD3ζ, via a direct physical interaction, as demonstrated by Far-Western blot. CrkII binding to CD3ζ could also be demonstrated in a heterologous system, where coexpression of a catalytically active Lck was used to phosphorylate the CD3ζ chain. TCR activation-induced Crk binding to CD3ζ resulted in increased and prolonged phosphorylation of CD3ζ, as well as ZAP70 and LAT, suggesting a positive role for CrkI/II binding to CD3ζ in regulation of TCR-coupled signaling pathways. Furthermore, Crk-dependent increased phosphorylation of CD3ζ coincided with inhibition of TCR downmodulation, supporting a positive role for Crk adaptor proteins in TCR-mediated signal amplification.



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Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial-mesenchymal transition and promotes stemness in mammary epithelial cells

Publication date: Available online 10 May 2017
Source:Cellular Signalling
Author(s): Eunhye Oh, Ji Young Kim, Daeil Sung, Youngkwan Cho, Nahyun Lee, Hyunsook An, Yoon-Jae Kim, Tae-Min Cho, Jae Hong Seo
Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that regulates Axin stability and plays a critical role in Wnt/β-catenin signaling. We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT) induction and its effects on mammary epithelial stem cells. USP34 expression levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced EMT, as evidenced by the upregulation of EMT markers including N-cadherin, phospho-Smad3, Snail and active-β-catenin, as well as the downregulation of Axin 1 and E-cadherin. USP34 knockdown (KD) in these cells also resulted in the acquisition of invasive behavior, and promoted stemness as indicated by enhanced mammosphere-forming ability, concomitant with the upregulation of Nanog, Oct4 and Sox2 mRNA expression. Endogenous USP34 expression was observed to be at low levels in virgin mouse mammary glands in vivo. When USP34-KD cells were transplanted into the cleared mammary fat pads (CFP) of mice, these cells reconstituted the mammary gland with ductal tree development within 3months. Our findings suggest a previously unknown role for USP34 in mammary gland development.



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Neuroprotective effect of salvianolate lyophilized injection against cerebral ischemia in type 1 diabetic rats

Salvianolate lyophilized injection (SLI) has been clinically used in China for the treatment of acutely cerebral infarction. Clinical and experimental studies have shown that Diabetes mellitus (DM) not only in...

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In-flight allergic emergencies

Allergic and hypersensitivity reactions such as anaphylaxis and asthma exacerbations may occur during air travel. Although the exact incidence of in-flight asthma and allergic emergencies is not known, we have...

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Re “International survey on skin patch test procedures, attitudes and interpretation” L.K. Tanno et al., WAOJ (2016) 9:8

A previous survey on the practice of diagnostic patch testing among representatives of member societies of the World Allergy Organization (WAO) has, in some countries, not addressed those stakeholders actually...

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Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities

Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a ...

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International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allerg...

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Asthma control in primary care: the results of an observational cross-sectional study in Italy and Spain

Poor asthma control observed in several surveys may be related to a lack of systematic assessment by physicians and/or to patient underestimation of symptoms. Along this line, the purpose of this study was to ...

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Blindness

Blindness: Loss of useful sight. Blindness can be temporary or permanent. Damage to any portion of the eye, the optic nerve, or the area of the brain responsible for vision can lead to blindness. There are numerous (actually, innumerable) causes of blindness. The current politically correct terms for blindness include visually handicapped and visually challenged.



MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Mechanisms and Dynamics of T Cell-Mediated Cytotoxicity In Vivo

Publication date: Available online 9 May 2017
Source:Trends in Immunology
Author(s): Stephan Halle, Olga Halle, Reinhold Förster
Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates. A better understanding of these factors is required to predict protective CD8 T cell immunity in vivo and to design optimized vaccination protocols.



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Sex differences in avoidance behavior after perceiving potential risk in mice

Sex has been considered as a potential factor regulating individual behaviors in different contexts. Recently, findings on sex differences in the neuroendocrine circuit have expanded due to exact measurements ...

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Interaction between cytochrome P450 2A6 and Catechol-O-Methyltransferase genes and their association with smoking risk in young men

Although some effects of gene–gene interactions on nicotine–dopamine metabolism for smoking behavior have been reported, polymorphisms of cytochrome P450 (CYP) 2A6 and catechol-O-methyltransferase (COMT) have not...

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Effects of GABAB receptors in the insula on recognition memory observed with intellicage

Insular function has gradually become a topic of intense study in cognitive research. Recognition memory is a commonly studied type of memory in memory research. GABABR has been shown to be closely related to mem...

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Brain structural investigation and hippocampal tractography in medication overuse headache: a native space analysis

Spatial normalization of brain images, a prerequisite for voxel based morphometry analysis, may account for the large variability of the volumetric data in medication overuse headache (MOH); possibly because t...

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Cognitive-enhancing and antioxidant activities of the aqueous extract from Markhamia tomentosa (Benth.) K. Schum. stem bark in a rat model of scopolamine

Plants of the genus Markhamia have been traditionally used by different tribes in various parts of West African countries, including Cameroun. Markhamia tomentosa (Benth.) K. Schum. (Bignoniaceae) is used as an a...

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Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial

Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20%), severe (≥20% biopsy cores)]. Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had reduced presence of acute inflammation [OR, 0.79; 95% confidence interval (CI), 0.63–0.99] and were less likely to have severe acute inflammation (OR, 0.66; 95% CI, 0.45–0.97), but there were no other associations between lipids and inflammation. Statin users had reduced presence of chronic inflammation (OR, 0.81; 95% CI, 0.69–0.95) and were less likely to have severe chronic (OR, 0.80; 95% CI, 0.68–0.95) and severe acute inflammation (OR, 0.73; 95% CI, 0.53–1.00), relative to non-users. Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk. Cancer Prev Res; 1–7. ©2017 AACR.



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Quality of life of depressed and suicidal patients seeking services from traditional and faith healers in rural Kenya

In rural Kenya, traditional and faith healers provide an alternative pathway to health care, including mental health care. However, not much is known about the characteristics of the populations they serve. Th...

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Tinnitus functional index: validation of the German version for Switzerland

Different standardized questionnaires are used to assess tinnitus severity, making comparisons across studies difficult. These questionnaires are also used to measure treatment-related changes in tinnitus alth...

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Reliability analysis of the Chinese version of the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) scale based on multivariate generalizability theory

The Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu) scale, a leukemia-specific instrument for determining the health-related quality of life (HRQOL) in patients with leukemia, had been developed an...

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