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1、会计学1抑郁焦虑障碍的诊断治疗专家共识耿德抑郁焦虑障碍的诊断治疗专家共识耿德勤徐州医学院附属勤徐州医学院附属第1页/共58页n抗抑郁剂的药物相互作用第2页/共58页流行病学流行病学第3页/共58页1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,20
2、02,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5 Pohjasvaara T, Leppavuori A,Siira I,
3、et al. Frequency and clinical determinants of poststroke depression. Stroke,1998,29:2311-2317.6 Hackett ML, Yapa C, Parag V, et al. Frequency of depression after stroke:A systematic review of observational studies. Stroke,2005,36:1330-1340.第4页/共58页害(VCI)者的抑郁症状的发生率约为40%60%nMCI的抑郁累计患病率约为26%1 Holtzer R
4、, Scarmeas N, Wegesin DJ, et al. J Am Geriatr Soc,2005,53:2083-2089.2 Modrego PJ, Ferrndez J. Arch Neurol,2004,61:1290-1293.3. Potter GG, Steffens DC. Contribution of depression ,Neurologist,2007,13: 105117. 第5页/共58页1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr
5、 Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disea
6、se, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry,2002,72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease:. Neurology, 2002,58(Suppl 1):S63S70.7. Eh
7、rt U,Aarsland D. Psychiatric aspects of Parkinsons disease. Curr Opin Psychiatry,2005,18: 335-341.第6页/共58页18.6%为广泛性焦虑、10%为惊恐发作1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars
8、 Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Kessler
9、 RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder:JAMA 2003,289:30953105.6. Janssens AC, Buljevac D, van Doorn PA. Prediction of anxiety and distress following diagnosis . Mult Scler,2006 ,12:794-801.7. Siegert RJ,Abernethy DA. Depression in multiple sclerosis: a review
10、. J Neurol Neurosurg Psychiatry,2005,76;469-475.第7页/共58页1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in
11、neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Lambert M, Robertson M. Depression in epilepsy: etiology, phenomenology and t
12、reatment. Epilepsia,1999,40(suppl 10):S21S47.6. Gaitatzis A,Trimble MR,Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurologica Scandinavica,2004,110:207-220.第8页/共58页1 Radat F,Swendsen J. Psychiatric comorbidity in migraine: a review. Cephalalgia,2005,25:165-178.2 Wang SJ,Juang KD,Fuh JL
13、,et al. Psychiatric comorbidity and suicide risk in adolescents with chronic daily headache. Neurology, 2007,68:14681473.第9页/共58页第10页/共58页神经系统疾病伴发抑郁焦虑障碍的特点神经系统疾病伴发抑郁焦虑障碍的特点第11页/共58页第12页/共58页第13页/共58页海马海马杏仁核杏仁核扣带回扣带回 皮质皮质前额叶前额叶皮质皮质第14页/共58页38 Female Outpatients With Recurrent Depression in Remission*
14、Significant inverse relationship between total hippocampal volume and the length of time depression went untreated.Sheline YI, et al. Am J Psychiatry. 2003;160:1516-1518.海马总体积海马总体积( mm3)未治疗的抑郁未治疗的抑郁R2=0.28 P=0.0006*01,0002,0003,0004,0003,0003,5004,0004,5005,0005,5006,000R2=0.28P=0.0006*第15页/共58页目前主要
15、神经生物学假设目前主要神经生物学假设/发现发现-3(形态学)(形态学) 抑郁症与细胞凋亡抑郁症与细胞凋亡BDNF=brain-derived neurotrophic factor.1. Sapolsky RM. Arch Gen Psychiatry. 2000;57:925-935.2. Duman RS, et al. Biol Psychiatry. 2000;48:732-739.应激应激2糖皮质激素糖皮质激素BDNF正常存活和生长正常存活和生长神经元的萎缩神经元的萎缩/死亡死亡树突分支树突分支1第16页/共58页目前主要神经生物学假设目前主要神经生物学假设/发现发现-4(形态学)(
16、形态学)治疗能预防或逆转损伤吗?治疗能预防或逆转损伤吗?5-HT=serotonin; NE=norepinephrine; ECT=electroconvulsive therapy. 1. Sapolsky RM. Arch Gen Psychiatry. 2000;57:925-935.2. Duman RS, et al. Biol Psychiatry. 2000;48:732-739.应激应激2糖皮质激素糖皮质激素BDNF正常存活和生长正常存活和生长神经元萎缩神经元萎缩/死亡死亡BDNF增加存活和生长增加存活和生长5-HT and NE,DA糖皮质激素糖皮质激素?药物治疗药物治疗,
17、 ECT, 心理治疗心理治疗2树突分支树突分支1第17页/共58页下丘脑下丘脑杏仁核杏仁核蓝斑蓝斑ACTH细胞因子细胞因子可的松可的松骨骨脂肪组织脂肪组织肾上腺肾上腺前额叶皮前额叶皮层层躯体感觉躯体感觉/情绪情绪心血管心血管代谢代谢免疫与神经元再激活免疫与神经元再激活认知认知肾上腺素肾上腺素, NE骨质疏松症骨质疏松症OConnor,etal.QJM2000;93:323-33Miller,OCallaghan.Metabolism2002:51:5-10第18页/共58页第19页/共58页第20页/共58页PSD虽然常见,但由于患者常有失语、忽略或认知损害虽然常见,但由于患者常有失语、忽略或
18、认知损害而不被诉说或识别而不被诉说或识别1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. C
19、urr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry,2002,72:1221.6. Oku
20、n MS, Watts RL. Depression associated with Parkinsons disease:. Neurology, 2002,58(Suppl 1):S63S70.第21页/共58页l皮质下小血管病性皮质下小血管病性VaD或或VCI患者的抑郁患者的抑郁障碍持续时间长、难治障碍持续时间长、难治. 突出表现:始动性突出表现:始动性差、精神运动迟缓和易伴执行功能障碍差、精神运动迟缓和易伴执行功能障碍lAD伴发的抑郁障碍有随病程延长而逐渐减伴发的抑郁障碍有随病程延长而逐渐减少的趋势少的趋势1 Benedetti F, Bernasconi A,Pontiggia A.
21、 Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression
22、 in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry,2002,72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons diseas
23、e:. Neurology, 2002,58(Suppl 1):S63S70.第22页/共58页PD患者的情感障碍与脑内多种神经递质的改变有患者的情感障碍与脑内多种神经递质的改变有关关1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:2
24、13-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry
25、 of the basal ganglia. J Neurol Neurosurg Psychiatry,2002,72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease:. Neurology, 2002,58(Suppl 1):S63S70.第23页/共58页MS患者的抑郁可能与病灶部位(额叶、颞叶)及炎患者的抑郁可能与病灶部位(额叶、颞叶)及炎症有关症有关l抑郁可为癫痫发作和发作后表现,但更多见于发作间期。l颞叶癫痫和左侧痫灶者容易发生抑郁。抑郁与癫痫的关系是双向的,病因多重而复杂抑郁与癫痫的
26、关系是双向的,病因多重而复杂1 Benedetti F, Bernasconi A,Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry,2006,19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry,2002,7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Op
27、in Psychiatry,2006,19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry,2005,76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry,2002,72:1221.6. Okun MS,
28、Watts RL. Depression associated with Parkinsons disease:. Neurology, 2002,58(Suppl 1):S63S70.第24页/共58页Kroenke K, et al. Arch Fam Med. 1994;3:774-779.神经科就诊抑郁焦虑患者特点神经科就诊抑郁焦虑患者特点不主动叙述情绪症状不主动叙述情绪症状多见主述为多见主述为睡眠问题睡眠问题、疲乏疲乏及不确定位置的及不确定位置的躯体疼躯体疼痛痛症状易与神经系统原发疾病相互影响,注意鉴别症状易与神经系统原发疾病相互影响,注意鉴别第25页/共58页Kroenke K,
29、et al. Arch Fam Med. 1994;3:774-779.0102030405060708090躯体症状的个数躯体症状的个数*抑郁患病率抑郁患病率(%)其他精神障碍情绪障碍(焦虑/抑郁)0 to 1(n=215)2 to 3(n=225)4 to 5(n=191)6 to 8(n=230) 9(n=139)*常见躯体症状常见躯体症状:l 头痛头痛l 头晕头晕l 疲乏疲乏l 失眠失眠l 背痛背痛l 四肢或关节痛四肢或关节痛l 月经紊乱月经紊乱l 消化道不适消化道不适l 腹痛腹痛l 胸痛胸痛l 性功能障碍性功能障碍多个多个躯体症状躯体症状可能预示可能预示抑郁症抑郁症第26页/共58页
30、第27页/共58页传导痛觉的颅神经和颈神经 直接受损或发生炎症 (神经炎性头痛)(神经炎性头痛) 头痛 颅外肌肉的收缩(紧张性或肌收缩性头痛)(紧张性或肌收缩性头痛) 颅内痛觉敏感组织被 牵引或移位(牵引性头痛)(牵引性头痛) 五官病变疼痛的扩散(牵涉性头痛)牵涉性头痛) 颅内外感觉敏感组织发生炎症 (如脑膜刺激性头痛)(如脑膜刺激性头痛) 颅内外动脉的扩张(血管性头痛(血管性头痛: :如偏头痛等)如偏头痛等) 精神因素(如焦虑、抑郁) 引起 (可能与疼痛耐受阈值降低有关)(可能与疼痛耐受阈值降低有关) 第28页/共58页ICHD-编码编码 WHO ICD10编码编码 诊断诊断 (英文原名,缩
31、写)(英文原名,缩写)1.G43偏头痛(偏头痛(Migranine)2.G44.2紧张型头痛紧张型头痛(Tension-type Headache, TTH)3.G44.0丛集性头痛和其他三叉自主神经性头痛(丛集性头痛和其他三叉自主神经性头痛(Cluster headache and other trigeminal autonomic Cephalalgrias)4.G44.80其他原发性头痛其他原发性头痛(Other primary headaches):新症每日持续性头痛新症每日持续性头痛(New daily-persistent headache, NDPH)12.R51头痛由于精神疾
32、病头痛由于精神疾病(Headaches attributed to psychiatric disorder)第29页/共58页地区紧张性头痛偏头痛偏头痛非洲1.7 (1 study)4.0 (2 studies)亚洲2.2 (3 studies)10.6 (6 studies)欧洲3.4 (6 studies)13.8 (9 studies)北美2.2 (1 study)12.6 (8 studies)南美5.0 (2 studies)9.6 (10 studies)平均11.23.2第30页/共58页可忽视第31页/共58页第32页/共58页Kroenke K, et al. Arch F
33、am Med. 1994;3:774-779.0102030405060708090躯体症状的个数躯体症状的个数*抑郁患病率抑郁患病率(%)(%)其他精神障碍其他精神障碍情绪障碍(焦虑情绪障碍(焦虑/ /抑郁)抑郁)0 to 1(n=215)2 to 3(n=225)4 to 5(n=191)6 to 8(n=230) 9(n=139)常见躯体症状:l头痛l头晕l 疲乏l 失眠l 背痛/腹痛/胸痛/四肢关节痛l 月经紊乱l 消化道不适l 性功能障碍多个多个躯体症状躯体症状可能预示可能预示抑郁症抑郁症第33页/共58页第34页/共58页第35页/共58页神经系统疾病伴发抑郁焦虑障碍的治疗目标神经
34、系统疾病伴发抑郁焦虑障碍的治疗目标第36页/共58页第37页/共58页第38页/共58页Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl 5):28-34.抑抑郁郁症症状状的的严严重重程程度度临床治愈临床治愈症状最少或无症状症状最少或无症状 (HAM-D(HAM-D 7)7),至少,至少3 3个月个月痊愈痊愈症状最少或无症状症状最少或无症状 至少至少6 6个月个月正常人群正常人群HAM-DHAM-D 7 7治治疗疗第39页/共58页1.Clinical Practice Guideline No. 5: Depression in Primary Care
35、, 2: Treatment of Major Depression; 1993. AHCPR publication 93-0551.2. American Psychiatric Association. Am J Psychiatry. 2000;157(suppl4):1-45.3.Anderson IM, et al. J Psychopharmacol. 2000;14:3-20. 4.Reesal RT, Lam RW. Can J Psychiatry. 2001;46(suppl1):21S-28S.5.DSM-IV-TR. 4th ed. Washington, DC: A
36、merican Psychiatric Association; 2000. 6.Rush AJ, Trivedi MH. Psychiatr Ann. 1995;25:704-705, 709.第40页/共58页Ref: 3. Ferrier IN. Treatment of major depression: Is improvement enough ? J Clin Psychiatry 60(Suppl 6):10-14,1999有有 效效症状改善,但仍有症状改善,但仍有残余症状残余症状 情绪仍然低落情绪仍然低落 睡眠障碍睡眠障碍 缺乏工作能力缺乏工作能力 对各种活动失去兴趣对各种活
37、动失去兴趣HAM-DHAM-D分值下降分值下降 5050临床治愈临床治愈彻底消除残余症状彻底消除残余症状 临床症状消失临床症状消失 与正常人没有区别与正常人没有区别 返回工作岗位返回工作岗位HAM-DHAM-D分值分值 7 7第41页/共58页 Remission=Psychiatric Status Rating (PSR) 1 or 2.*Psychosocial functioning after treatment with sertraline or imipramine. P0.05 compared with the remission group.Miller IW, et a
38、l. J Clin Psychiatry. 1998;59:608-619.123自评社会适应量表自评社会适应量表 (平均平均 标准差标准差)无疗效无疗效改善改善临床治愈临床治愈健康对照健康对照(n=299)(n=122)(n=202)(n=482)第42页/共58页神经科抑郁焦虑障碍的药物治疗神经科抑郁焦虑障碍的药物治疗第43页/共58页第44页/共58页第45页/共58页第46页/共58页第47页/共58页第48页/共58页第49页/共58页第50页/共58页第51页/共58页第52页/共58页第53页/共58页第54页/共58页 在神经科处理精神症状时应注意以下几个问题在神经科处理精神症
39、状时应注意以下几个问题:v诊断是否正确诊断是否正确? ?v患者是否伴有精神病性症状患者是否伴有精神病性症状? ?v患者是否得到适当治疗患者是否得到适当治疗( (剂量及疗程剂量及疗程)?)?v不良反应是否影响达到有效治疗剂量不良反应是否影响达到有效治疗剂量? ?v患者依从性是否好患者依从性是否好? ?v药物使用方式是否合适药物使用方式是否合适? ?v治疗结果是如何评价的治疗结果是如何评价的? ?v是否存在影响疗效的躯体及精神病性障碍是否存在影响疗效的躯体及精神病性障碍? ?v是否存在其他干扰治疗的因素是否存在其他干扰治疗的因素? ?第55页/共58页欢迎来指导,谢谢欢迎来指导,谢谢第56页/共5
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43、Z3gtGT)anAN!4huHV-boBP$5irFS*8CP$5iwJW+cqDQ%6kxKX1erER*8lyLZ2fsFT(9mzN#3gtHU)aoBO!4ivIV-cpCP$6jwJW0dqDQ&7kxLY1erFS*8lzMZ2ftGT(9nAN#3huHU-boBO$5ivIW+cpCQ%6jwKX0dqER&7lyLY1fsFS*9mzMZ3gtGT)anAO!4huIV-boCP$5iwJW+cqDQ%6kxKXS*9mzM#3gtGU)anAO!4huIV-boCP$5iwJW+dqDQ%7kxKX1erER*8lyLZ2fsGT(9mAN#3guHU)aoBO!4ivI
44、V-cpCP%6jwJX0dqDR&7kxLY1erFS*8lzMZ2gtGT(anAN#4huHU-boBO$5ivIW+cpDQ%6jxKX0drER&7lyLY1fsFS*9mzM6jwJX0dqDR&7kxLY1erFS*8lzMZ2ftGT(anAN#4huHU-boBO$5ivIW+cpCQ%6jxKX0drER&7lyLY1fsFS*9mzMZ3gtGU)anAO!4huIV-boCP$5iwJW+dqDQ%7kxKX1erER*8lyLZ2fsFT(9mAN#3guHU)aoBO!4ivIV-cpCP$6jwrER*8lyMZ2fsGT(9mAN#3guHU)aoBO!5ivI
45、V+cpCP%6jwJX0dqDR&7kxLY1esFS*8mzMZ2gtGT(anAN#4huHU-boBP$5ivJW+cpDQ%6jxKX0drER&7lyLY2fsFS(9mzM#3gtGU)anAO!4huIV-bpCP$5jwJW+dqDQ%7kxKX1eHU-boBO$5ivJW+cpDQ%6vJW+cpDQ%6jxKX0erER&8lyLY2fsFS(9mzM#3gtGBP$5iwJW+cqDQ%6kxKX0erER&8lyLY2fsFT(9mzN#3gtHU)anBO!4hvIV-bpCP$6jwJW0dqDQ&7kxKY1erES*8lyMZ2ftGT(9nAN#3huHU
46、)boBO!5ivIV+cpCQ%6jwKX0dqER&7kyLY1esFS*9mzMZ3gtGT)anAN7kxKY1erES*8lyMZ2fsGT(9nAN#3huHU)boBO!5ivIV+cpCQ%6jwKX0dqEP$5iwJW+cqDQ%6kxKX0erER&8lyLZ0dqDQ&7kxLY1erFS*8lzMZ2ftGT(9nAN#3huHU-boBO$5ivIW+cpCQ%6jwKX0dqER&7lyLY1fsFS*9mzMZ3gtGT)anAN!4huIV-boCP$5iwJW+cqDQ%6kxKX1erER*8lyLZ2fsFT(9mzN#3gtHU)aoBO!4ivIV-
47、cpCP$6jwJ3gtGT)anAN!4huIV-boCP$5iwJW+cqDQ%6kxKX0erER*8lyLZ2fGT)anAO!4huIV-boCP$5iwJW+cqDQ%6kxKX1erER*8lyLZ2fsFT(9mzN#3gtHU)aoBO!4ivIV-cpCP$6jwJW0dqDQ&7kxLY1erFS*8lzMZ2ftGT(9nAN#3huHU-boBO$5ivIW+cpCQLY1erFS*8lzMZ2gtGT(anAN#4huHU-boBO$5ivIW+cpDQ%6jxKX0drER&7lyLY1fsFS*9mzM#3gtGU)anAO!4huIV-boCP$5iwJW+d
48、qDQ%7kxKX1erER*8lyLZ2fsGT(9mQ%6jxKX0drER&7lyLY1fsFS*9mzMZ3gtGU)anAO!4huIV-boCP$5iwJW+dqDQ%7kxKX1erER*8lyLZ2fsFT(9mAN#3guHU)aoBO!4ivIV-cpCP$6jwJX0dqDR&7kxLY1(9mAN#3guHU)aoBOZ2gtGT(anAN!4huHV-boBP$5ivJW+sGT(9mAN#3guHU)boBO!5ivIV+cpCP%6jwJX0dqDR&7kyLY1esFS*8mzMZ2gtGT(anAN#4huHV-boBP$5ivJW+cpDQ%6jxKX0dr
49、ER&8lyLY2fsFS(9mzM#3gtGU)anAO!4hLY1esFS*8mzMZ2gtGT(anAN#4huHU-boBP$5ivJW+cpDQ%6jxKX0drER&7lyLY2fsFS(9mzM#3gtGU)anAO!4huIV-bpCP$5jwJW+dqDQ%7kxKX1erES*8lyMZ2fsGT(9mAN#3guHU)aoBO!W+dqDQ&7kxKY1erES*8lyMZ2fsGT(9mAN#3huHU)boBO!5ivIV+cpC&7kxKY1erES*8lyMZ2fsGT(9nAN#3huHU)boBO!5ivIV+cpCQ%6jwKX0dqER&7kyLY1esF
50、S*8mzMZ3gtGT)anAN!4huHV-boBP$5ivJW+cqDQ%6kxKX0erEzMZ3gtGT)anAN!4huIV-boCP$5iwJW+cqDQ%6kxKX0erER*8lyLZ2fsFT(9mzN#3gtHU)anBO!4ivIV-cpCP$6jwJW0dqDQ&7kxKY1erFS*8lzMZ2ftGT(9nAN#3huHU)boBO$5yLZ2fsFT(9mzN#3gtHU)anBO!4hvIV-cpCP$6jwJW0dqDQ&7kxKY1erES*8lzMZ2tHU)anBO!4ivIV-cpCP$6jwJW0dqDQ&7kxKY1erFS*8lzMZ2ftGT(9nAN#3huHU)boBO$5ivIW+cpCQ%6jwKX0dqER&7
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