【作者】 常学润；

【导师】 薛付忠； 张敬悬；

【作者基本信息】 山东大学 ， 流行病与卫生统计学（专业学位）， 2013， 硕士

【摘要】 [目的]癫痫是世界范围内的常见病和多发病,长期的痫性发作严重影响了患者的生活质量,使患者躯体和精神疾病发病率增加,也给家庭和社会增加了沉重的经济负担。目前,癫痫的发病人数多,治疗缺口大,社会公众对癫痫患者普遍存在歧视,癫痫患者及家属对疾病的性质、治疗方法以及生活中的注意事项等知之甚少,农村三级医疗保健网的医务人员也缺乏科学的认识、诊断、治疗方法很不规范,病人有病乱投医,花费大量时间和金钱,癫痫仍然得不到有效控制。本文主要拟完成以下目的：1)研究山东省癫痫病人利用苯巴比妥治疗的疗效、不良反应以及影响因素。2)通过研究积累经验,进一步大面积推广苯巴比妥治疗的方法。3)通过对基层卫生人员短期培训,进一步了解管理和治疗病人的可行性。[方法]采用随机抽样方法,随机抽取了山东省三个县804例惊厥型癫痫患者,对其进行入组管理,由经过严格培训的乡镇卫生人员进行随访和治疗。在随访过程中分别填写惊厥型癫痫病例筛查诊断表和医生随访表,我们利用填写的内容做出分析。[结果]1.入组干预治疗对象的基线状况描述：1.1病人基本情况三个县筛查符合入组标准的癫痫患者804例。其中男性434例,女性370例。患者的平均发病年龄(39.07±16.17)岁,年龄的中位数为38.00岁。三个县筛查入组的患者中,首发年龄在18.36±14.44岁,大多数患者首发年龄集中在15.00岁左右；近一年的发作次数为19.65±39.25,中位数为10.00次。1.2病人曾就诊医疗机构三县的癫痫病人在过去就诊的医疗机构有个体诊所、乡镇医院、县级医院、市级医院,其中在县级医院确诊的病人最多,占总病例数的54.10%,其次是市级医院,确诊的病人占总病例数的50.50%,乡镇医院、个体诊所确诊的病例数较少,分别为31.72%和24.75%(同一病人有可能在不同医疗机构就诊)。1.3病人曾用过的诊疗方法过去曾用过的诊断方法中,三县病人检查确诊采用的仪器有脑电图占66.45%,CT检查占13.37%,核磁共振检查占0.26%,未作任何仪器检查的病人为19.92%。过去曾用过的治疗方法中使用西药治疗的病人居多占81.34%,其中主要为苯妥英钠(42.29%),苯巴比妥(27.45%),卡马西平(22.26%),丙戊酸钠(1.19%),苯妥英钠每日剂量为309.03±177.74mg,大多数病人剂量集中在300mg；苯巴比妥每日剂量为114.74±103.12mg,中位数为90mg；卡马西平每日剂量为313.37±158.66mg,大多数病人剂量集中在300mmg；丙戊酸钠每日剂量为512.16±239.00mg,中位数为600mg。另外,其他治疗方法还有中药、针灸、割治、埋线、民间验方,它们占所有治疗方法的18.66%。1.4病人过去治疗规律状况近期三县癫痫病人服药很不规律,有些病人从未接受过任何治疗。服药不规律与从未接受治疗的癫痫病人占总入组人数的83.21%,其中,A县入组的全部病人(428例)均存在服药不规律(84.11%)和从未接受治疗(15.89%)；C县服药不规律的癫痫病人数位80例(占58.39%),从未接受治疗的病人57例(占41.61%)。在这种治疗状况下,大多数癫痫病人每月发作集中在2次(中位数),每年发作集中在10次(中位数),每年平均只有1个月不发作,其余月份均有发作2.患者随访观察2.1疗效观察以发作次数为标准,苯巴比妥剂量达到维持剂量后,病人一年内发作次数与以前12个月相比,三县癫痫病人在观察期内显效率占65.82%,有效率占11.77%,无效率占10.76%,恶化率占11.65%,经非参数秩和检验发现,三县的疗效分布不同。B县显效率最高,为79.04%,A县、C县显效率分别为65.81%、43.28%。三县癫痫病人服用单药苯巴比妥剂量平均为76.30-35.50mg,中位数为60mg,其中A县和C县中位数均为60mg,B县为120mg.患者自我感觉的考察项中,感觉好一些的患者占44.86%,感觉没有变化的患者占52.38%,感觉更差的患者占2.76%其中,B县患者感觉好一些的比例最高,占77.87%。C县和A县感觉疗效没有变化的患者占比较高,分别为87.14%、58.39%。2.2不良反应分析三县癫痫病人服用苯巴比妥的综合分析判断,发现本药引起的不良反应较轻,占82.35%的病人无不良反应发生,占16.15%的病人有轻度不良反应,占1.50%病人仅有中度不良反应,重度不良反应者可忽略不计。其中A县无不良反应发生率为71.87%,B县为99.15%,C县为85.82%。轻度不良反应发生率A县为25.53%,B县为0.43%,C县为14.18%。中度与重度的不良反应极其少见。在轻度不良反应中出现最多的是困倦、嗜睡,A县发生率为46.10%,B县发生率为2.13%,C县发生率为24.82%。其次是头晕,A县发生率为16.55%,B县发生率为0.43%,C县发生率为10.64%。其余的轻度不良反应发生率从重到轻依次为头痛、共济失调、消化道症状、忧郁、焦虑、多动,皮疹发生最少。2.3患者依从性判断医生对三县癫痫患者依从性的判断根据预计剩余药片数和实际剩余药片数的比较,发现遵从医嘱良好的患者占95.37%,不好者占4.63%。3疗效影响因素分析先对惊厥型癫痫病例筛查诊断表和医生随访表出现的各因素进行赋值,再研究各因素与疗效的关系,利用统计学方法,进行了单因素logistic分析和多因素logistic分析。在单因素logistic分析中,按α=0.05水准,筛选出有统计学意义的变量为Q13(发作时是否有大小便失禁),Q2(苯巴比妥剂量),QC4(转为全身发作),Q7(医生对患者总体依从性判断),Q72(实际剩余药片数)；在多因素logistic分析中,使用逐步回归,筛选出身高、发作类型、以前有无治疗经历和依从性为苯巴比妥疗效的影响因素。其中,以前有无治疗经历是影响苯巴比妥疗效的最大危险因素,其比值比OR为8.399,其次,身高是影响苯巴比妥疗效的第二危险因素,它的比值比OR为1.018,再次,发作类型和依从性影响疗效的比值比OR为0.691和0.409,通过进一步观察,发现全身强直-阵挛类型、无治疗经历患者、依从性好的患者疗效较好.[结论]1.苯巴比妥能有效控制惊厥型癫痫、不良反应少而轻微,可以在山东省全面推广。也可以向以惊厥型癫痫为发作类型的其它地区推广。2.影响苯巴比妥疗效的因素为患者的身高、发作类型、过去是否曾治疗过以及依从性。3.通过短期培训方式,基层卫生人员可以承担起宣教、治疗、随访的任务。更多还原

【Abstract】 ObjectiveEpilepsy is both common disease and frequently-occurring disease in the world and its long-tem seizure make patients’ living quality worsen, make patients’ morbidity for body and mental disease go up, make health-care costs and the financial burden for families and societies increase. At present, There are a number of epilepsy patients and treatment gap. The public commonly discriminate against epilepsy patients, meanwhile, People with epilepsy and their family members know little about the nature and treatment methods for epilepsy or the dos and don’ts on life. Medical workers in three-level health care network are short of scientific cognition and diagnoses and treatment methods. Therefore, patients spend much time and money seeking help for the doctors, but patients’ condition were not under control.The thesis would achieve the following objectives:1. To explore the curative effects and adverse reaction and influencing factors of phenobarbital in the treatment of generalized tonic clonic seizure (GTCS) cases in Shandong Province.2. To gather experience and widely spread the treatment methods for phenobarbital3. To further study the feasibility of manage and treatment for convulsive epilepsy by a short-term train for primary health workers.Methods Patients with convulsive epilepsy in the three county of Shandong province were randomly identified as the study subjects by using stratified and cluster sampling approach. Local primary health workers, who were provided with special training, carried out screening, treatment, and follow-up. During the intervention, a form for doctor and a form for patients will be filled in as source material. Then we analyze these data again. Results1. The baseline data of sample1.1Basic information of the patients804patients with convulsive epilepsy in three counties were found conformed to the standards. There were434men and370women in the group. The average diagnostic age of the patient was (39.07±16.17), the median was38years old. The age of onset was (18.36±14.44). Most patients age distributed in15years old. The frequency of attacks was (19.65±39.25) in the lasted one years and the median was10.1.2Medical institutions where the patients used to goThe medical institutions where the epileptic patients were made a definite diagnosis were individual clinics, county hospitals, township hospitals, municipal hospitals in the three counties in the past. The most patients were diagnosed in the county hospitals, accounting for54.10%of the total cases. Secondly, municipal hospitals accounted for50.50%. Township hospitals and individual clinics had31.72%and24.75%patients respectively. The same patients can be diagnosed in different medical institutions.1.3Diagnostic and therapeutic methods used by the patientsThe instruments used to be diagnosed were electroencephalogram (66.45%), CT (13.37%), nuclear magnetic resonance (0.26%), nevertheless,19.92%patients did not do any examinations. Western medicine, including Phenytoin sodium (42.29%), phenobarbital(27.45%), carbamazepine (22.26%), valproic acid sodium (1.19%), were the main treatment methods in the past. It accounted for81.34%among all the methods. In detail, The daily dose of phenytoin sodium was (309.03±177.74)mg and most patients daily dose concentrated in the300mg. Phenobarbital daily dose was (114.74±103.12)mg, and the median dose was90mg. The daily dose of carbamazepine was (313.37±158.66) mg and most concentrated in the300mg. Valproic acid sodium daily dose was (512.16±239.00) mg, and the median dose was600mg. In addition, other treatment like Chinese medicine, acupuncture, Gezhi, buried line and folk prescription accounted Diagnostic and therapeutic methods used by the patients for18.66%among all the methods.1.4Whether or not to take medicine regularlyRecently, some epileptic patients in three counties did not take medicine regularly, and others patients had never taken any medicine or even received any treatment. The patients, who took medicine irregularly and did not receive any treatment, accounted for83.21%. Then, the patients who did not take medicine regularly accounted for84.11%and the patients who did not received any treatment accounted for15.89%in all the428patients in A county.80patients did not have medicine regularly in C county, accounting for58.39%.57patients had never received medicine therapy accounting for41.61%. At this kind of conditions, most epilepsy attack focused on2times a month and10times a year. On average, only one month the patients did not have epilepsy attack and the rest of the month the patients had the trouble of epilepsy.2. patients’follow-up2.1curative observation After the patients from three counties attaining the phenobarbital maintenance dosage for12months, the obvious effects rate was65.82%, effective rate was11.77%, invalid rate was10.76%and the deterioration rate accounted for11.65%, which the result was assessed by seizures frequency. There are many obvious differences in efficacy among three counties by testing nonparametric one-way ANOVA, which the obvious effects rate in B county is79.04%and65.81%in A county,43.28%C in county. The average maintenance doses for patients were76.30±35.50mg and the median was60mg. Particularly, the median in A county is60mg and in B county is120mg. Another important outcome was the subjective feeling of patients. The patients felt better in44.86%, no change in52.38%and worse in2.76%. Especially the highest rates of feeling better is77.87%, which the patients were from B county. However, the patients feeling no change was87.14%in C county and58.39%in A county.2.2the analysis of adverse reactions The ADR in Phenobarbital is light according to a synthesis of this study, nearly no heavy bad reaction, only1.50%in patients was moderate bad reaction and16.15%was mild. The most patients (82.35%) feel no adverse reactions. Especially, in A county, B county and C county, there were71.87%,99.15%and85.82%in patients feeling no adverse reactions. About the mild adverse reactions, most was sleepy or drowsiness, differently in A county was16.55%, B county was0.43%and C county was10.64%. Others were mild adverse reactions like headache, ataxia, gastrointestinal symptoms, depression, anxiety, hyperactivity and rash as severity ranking.2.3patient compliance Local heath workers assessed patient compliance according to the comparison of the remaining number of tablets is expected and actual number of remaining tablets. The result was good in95.37%and not good in4.63%.3. The analysis of influencing factors of efficacy According to the follow-up form for doctor and the screening form for convulsive epilepsy patients, we found the possible influencing factors and assign them. Then, the data analysts used univariate and multivariate logistic regression analyses for them. In univariate logistic analyses(α=0.05), Statistically significant variables are Q13(Seizures were incontinent or not), Q2(doses of phenobarbital), QC4(change to generalized seizures), Q7(patient compliance judged by local health workers), Q72(The actual remaining number of tablets) However, in multivariate logistic regression analyses, using stepwise regression, the height, seizure type, treatment history and compliance were the influencing factors of efficacy. Especially, the treatment history is the most significant risk factor (OR=8.399), the second is height (OR=1.018), the third is seizure type (OR=0.691) and the compliance is the last (OR=0.409). Through further observation, found that patients with generalized tonic-clonic type, without the experience of treatment, good compliance had good efficacy.Conclusions1. Phenobarbital has a good curative effects and mild adverse reactions for Patients with convulsive epilepsy. Its treatment methods can be widely introduced in Shandong province and also in the other area with the type of convulsive epilepsy.2. The influencing factors, which phenobarbital treated convulsive epilepsy, were patients" height, epileptic seizure type, ever be treated in the past and patients’ compliance.3. By a short-termed training, primary health workers can take on missions, follow-ups and treatments.更多还原