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    Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis
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    Abstract:
    BACKGROUND: Intralymphatic immunotherapy (ILIT) is a new route of allergen-specific immunotherapy. Data confirming its effect is restricted to a small number of studies. METHODOLOGY: A systematic review with meta-analysis was conducted. The short-term (less than 24 weeks), medium-term (24-52 weeks), and long-term (more than 52 weeks) effects of ILIT in patients with allergic rhinoconjunctivitis (ARC) were assessed. The outcomes were combined symptom and medication scores (CSMS), symptoms visual analog scale (VAS), disease-specific quality of life (QOL), specific IgG4 level, specific IgE level, and adverse events. RESULTS: Eleven randomized controlled trials and 2 cohorts (483 participants) were included. Compared with placebo, short term benefits of ILIT for seasonal ARC improved CSMS, improved VAS and increased specific IgG4 level but did not change QOL or specific IgE level. Medium-term effect improved VAS. Data on the long-term benefit of ILIT remain unavailable and require longer term follow-up studies. There were no clinical benefits of ILIT for perennial ARC. ILIT was safe and well-tolerated. CONCLUSION: ILIT showed short-term benefits for seasonal ARC. The sustained effects of ILIT were inconclusive. It was well tolerated.
    痛みや眠気の測定法としてVisual Analogue Scale(VAS)がある。VASは,紙での実施が一般的で,手軽にオンライン質問紙が作成できるGoogleフォームに追加できるものは見当たらない。筆者らは,Googleフォームに埋め込み可能な「動画」を応用したVAS(O-VAS)を制作し,男女21名に,1日のうちの4時点で,ラジオボタン(11件法)や数値入力(101件法),紙媒体のVASと併用して主観的眠気を評価してもらい,比較した。その結果,1試行目をのぞき,O-VASはラジオボタン,数値入力,紙のVASとおおむね0.9以上の高い相関を示し,特に数値入力との間で最も安定して高い相関が示された(rs>.94)。一方で,従来の紙のVASはラジオボタンとの間で最も安定して高い相関が示された(rs>.98)。また,O-VASはラジオボタンと数値入力よりも有意に回答しにくいことが示された(ps<.05)。O-VASは数値化しにくい構成概念を評定する際の代替法として用いることができる可能性が示唆された一方で,回答のしやすさの面で課題が残された。
    In 459 migraine attacks, information provided to patients (from negative to neutral to positive) modified placebo and medication outcomes in a progressive fashion.
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    Σκοπός:Ο βασικός σκοπός της μελέτης ήταν να ελεγχθεί αν ο συνδυασμός γκαμπαπεντίνης (600mg 4ώρες προεγχειρητικά, 600mg 24ώρες μετά), κεταμίνης (0.3mg/kg πριν την αναισθησία), λορνοξικάμης (8mg πριν την αναισθησία και 8mg/12ώρες) και τοπικής έγχυσης ροπιβακαΐνης (5ml 7.5% στα σημεία εισόδου των trocar) έχει καλύτερη αναλγητική δράση σε σχέση με το καθένα από αυτά τα φάρμακα ξεχωριστά τις πρώτες 24 ώρες μετά από λαπαροσκοπική χολοκυστεκτομή. Δευτερεύων σκοπός ήταν να εξετασθεί αν αυτός συνδυασμός έχει λιγότερες επιπλοκές σχετιζόμενες με την κατανάλωση οπιοειδών.Μέθοδος:Διεξήχθη μία ελεγχόμενη τυχαιοποιημένη μελέτη σε 2 νοσηλευτικά κέντρα. 148 ασθενείς ηλικίας 18-70 ετών κατανεμήθηκαν τυχαία σε 6 ομάδες (28 σε κάθε ομάδα) με τη χρήση λογισμικού: A (γκαμπαπεντίνη/κεταμίνη/λορνοξικάμη/ροπιβακαΐνη), B (γκαμπαπεντίνη/placebo/placebo/placebo), Γ (placebo/κεταμίνη/placebo/placebo), Δ (placebo/placebo/λορνοξικάμη/placebo), E (placebo/placebo/placebo/ροπιβακαΐνη) και ΣΤ (placebo/placebo/placebo/placebo). Μόνο ο κύριος ερευνητής γνώριζε την ομάδα κάθε ασθενούς και παρείχε τα φάρμακα και τα εικονικά φάρμακα σε καλυμμένες προγεμισμένες σύριγγες. Η κύρια έκβαση της μελέτης ήταν η 24ωρη κατανάλωση μορφίνης. Δευτερεύουσες εκβάσεις ήταν η συχνότητα των σχετιζόμενων με τα οπιοειδή επιπλοκών (ναυτία, έμετος, καταστολή, κνησμός και δυσκολία ούρησης).Αποτελέσματα:Μόνο οι ομάδες Α (6.4mg), B (9.46mg) και Δ (9.36mg) είχαν χαμηλότερη κατανάλωση μορφίνης σε σχέση με την ομάδα ελέγχου (20.29mg) (p<0.001, p=0.01 και p=0.008 αντίστοιχα). Η ομάδα Α δε διέφερε από τις ομάδες Β και Δ (p=0.92, p=0.93). Υπήρξε διαφορά μόνο στα επεισόδια ναυτίας και μόνο μεταξύ των ομάδων Α (n=5) και της ομάδας ελέγχου (n=12) (p=0.018). Συμπεράσματα:Ο συνδυασμός γκαμπαπεντίνης, κεταμίνης, λορνοξικάμης, και τοπικής έγχυσης ροπιβακαΐνης δεν έχει ισχυρότερη αναλγητική δράση σε σχέση με μόνη την γκαμπαπεντίνη ή τη λορνοξικάμη μετά από λαπαροσκοπική χολοκυστεκτομή. Ο συνδυασμός μειώνει μόνο τη συχνότητα της μετεγχειρητικής ναυτίας αλλά απαιτούνται μεγαλύτερες μελέτες για την εξαγωγή ασφαλών συμπερασμάτων.
    Placebo group
    Placebo response
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    【背景】アレルギー性鼻炎 (AR) の重症度や症状の程度を評価する目的で, Allergic Rhinitis and its Impact on Asthma (ARIA) やわが国の鼻アレルギー診療ガイドライン (PG-MARJ) に基づく質問票が用いられている. しかし, ARIAでは患者の多くが中等症・重症と分類されてしまい, PG-MARJでは症状を1日の平均回数でスコア化しており, 正確に回数を把握するのが困難であるという問題点がある. 【目的】小児AR患者の重症度および症状の程度の評価, モニタリングのため, より簡便な方法であるvisual analog scale (VAS) の有用性を検討する. 【対象・方法】当科定期受診したAR患者を対象とし, ARIAならびにPG-MARJに基づく質問票と鼻炎症状のVASを比較検討した. また, 1~2か月後の再診時までのそれぞれの変化について検討した. 【結果】VAS値は, ARIAの分類による軽症よりも中等症/重症で有意に高値であり, 両者を識別するカットオフ値は26mmであった. また, VAS値はPG-MARJによる症状の程度と有意な正の相関を認め, さらに再診時までの鼻炎症状点数の変化量はVASの変化量との間に有意な正の相関を認めた. 【結論】小児AR患者では, VASは重症度ならびに症状の程度を簡便に評価することが可能であり, 症状のモニタリングのツールとして有用である可能性が示唆された.
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    While ethics of placebo use has been debated since discovery of the phenomena, there has yet to be a study that examines the aftereffect of individuals learning of a personal placebo response on their future ability to experience a placebo response. In the first study, eleven participants diagnosed with irritable bowel syndrome in a placebo study were interviewed individually about their personal placebo response. We found no changes in attitudes about the likelihood of using medical and non-medical treatments for pain, likelihood of participating in future studies or likeability and trust of experimenters. In addition, we found no changes in mood except for a slight improvement in frustration. In the second study, 77 undergraduate students from the University of Florida were divided into three conditions: placebo, control and repeated baseline. We used a double placebo design with verbal placebo suggestion and conditioning to induce a placebo response and to examine the effect of providing information about a participant's personal placebo response on their future placebo response. Using a heat thermode, we discovered that there were no differences in future pain responding between participants who were told that they experienced a placebo response versus those who were not. In addition, similar to the first study, we found no detrimental effects of the placebo information variables measured. These studies suggest the placebo response persists even after revelation of a personal placebo response and placebo use does not appear to cause adverse effects on mood and other attitude variables assessed.
    Placebo response
    Nocebo
    Nocebo Effect
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    To examine whether there are gender differences in event-related potential (ERP) responses to painful stimulation after administration of placebo medication; and to investigate whether placebo medication reduces anticipatory stress and if this reduction can explain the placebo analgesic response. Several experimental and clinical studies have shown that males report lower pain compared with females. There are, however, few reports of gender differences in placebo analgesia.All subjects (n = 33; 17 women) participated in both a natural history and a placebo condition. ERPs were evoked by heat pulses with a peak at 52 °C.The results showed that pain unpleasantness and the N2/P2 ERP components were reduced in the placebo condition compared with the natural history condition. Only men displayed placebo responses in pain report and in the P2 component. Anticipatory stress was reduced after placebo administration, and the reduction in anticipatory stress was significantly related to the placebo effect on pain. Regression analyses revealed that the interaction of gender by anticipatory stress was significantly related to the mean placebo response, with men responding with lower stress after placebo medication, and larger placebo responses.A placebo response on pain unpleasantness was observed in men only, and reduced stress after placebo administration was observed in males only. Thus, reduced stress may be a mechanism for placebo responses in pain.
    Placebo response
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    Background The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established. This study defines changes in dosing of intravenous patient-controlled analgesia as a clinically relevant outcome and compares it with VAS measures of postoperative pain. Methods Visual analog scale measurements were obtained from 150 patients on the morning after intraabdominal surgery. On the same afternoon, 50 of the patients provided a VAS score on the same form used in the morning, 50 on a new form, and 50 were not asked for a second VAS measurement. Results Visual analog scale values and changes in value were similar for patients who were given a new VAS form in the afternoon and those who used the form that showed the morning value. The proportions of patients requesting additional analgesia were 4, 43, and 80%, corresponding to afternoon VAS scores of 30 or less, 31-70, and greater than 70, respectively. Change from morning VAS score had no apparent influence on patient-controlled analgesic dosing for patients with afternoon values of 30 or less or greater than 70, but changes in VAS scores of at least 10 did discriminate among patients whose afternoon values were between 31 and 70. Conclusions When pain is an outcome measure in research studies, grouping final VAS scores into a small number of categories provides greater clinical relevance for comparisons than using the full spectrum of measured values or changes in value. Seeing an earlier VAS form has no apparent influence on later values.
    A previous meta-analysis of clinical analgesic trial studies showed generally low magnitudes of placebo analgesia (N. Engl. J. Med. 344 (2001) 1594). However, as studies included in their analysis used only placebo as a control condition, we conducted two meta-analyses, one in which 23 studies used only placebo as a control condition, and one in which 14 studies investigated placebo analgesic mechanisms. Magnitudes of placebo analgesic effects were much higher in the latter (mean effect size=0.95) as compared to the former (mean effect size=0.15) and were significantly different (P=0.003). This difference as well as differences in effect sizes within studies of placebo mechanisms may be parsimoniously explained by differences in expected pain levels produced by placebo suggestions and by conditioning. Furthermore, some of the studies of placebo analgesic mechanisms indicate that the magnitude of placebo analgesia is higher when the placebo analgesic effect is induced via suggestion combined with conditioning than via suggestion alone or conditioning alone. Based on these findings, we suggest that placebo analgesic effects are most optimally conceptualized in terms of perception of the placebo agent, and therefore a new definition of placebo response is proposed.