基于行政管理数据识别慢性病发病病例背景下确定洗脱期时长最佳策略的系统综述

背景使用行政管理数据时,确立清晰、适当的慢性病洗脱期时长是正确确定反复就医的慢性病患者发病时点、确定新发病例的基础。目的通过系统文献回顾,综述确定洗脱期时长的方法,以期为我国研究者后续使用行政管理数据识别慢性病新发病例时确认洗脱期长短、正确识别新发病例提供思路。方法于2021年10月,系统检索PubMed、Web of Science、EmBase、中国知网、维普中文科技期刊全文数据库、万方知识服务平台,获取有关利用行政管理数据探究慢性病发病、患病情况的文献,检索时限均为建库至2022-10-01。由两名研究者独立筛选文献并提取相关信息,并采用定性研究报告评价标准(SRQR)评价文献方法学质量后,使用描述性分析法总结洗脱期时长的确定方法。结果共纳入26篇文献,纳入文献的SRQR评分均≥15分,方法学质量较好。文献所使用的数据主要来自加拿大、美国、澳大利亚等行政管理数据完整、丰富的国家(地区),聚焦的疾病包括糖尿病、肿瘤、精神分裂症等多种慢性病。研究指出,设定合适的洗脱期时长是准确识别发病病例的基础。目前,文献中确定洗脱期时长的方法主要包括直接限定法、一致性检验法和逆向生存函数法三大类,其中最常用的方法是直接限定法,逆向生存曲线法的使用率相对较低。结论直接限定法、一致性检验法和逆向生存函数法均有相应的优势和局限性,方法的选择标准、判断标准和稳定性有待进一步探究。

药物洗脱期对急性心肌梗死后进行运动试验患者的影响

Study objectives: Pharmacological therapy can reduce diagnostic and prognostic accuracy of exercise stress testing. However, the risk of withdrawing drugs ear ly after myocardial infarction (MI) has not been established. We assessed safety and clinical implications of drug withdrawal in patients undergoing stress test ing after uncomplicated MI. Methods: A total of 362 MI patients underwent ECG Ho lter recording before and after withdrawing beta blockers, calcium antagonists and nitrates. QRS(QRS/h) and ventricular premature beats(VPB/h) count per hour, repetitive ventricular arrhythmias, ST segment changes and patient complaints w ere evaluated for reproducibility using kappa statistics and Bland Altman metho d. Results: No major complications occurred. Forty three patients complained of >1 symptom on and 37 off therapy. QRS/h and VPB/h count were significantly(p< 0 .0001) higher off therapy but correlated with the corresponding values on therap y. A mean heart rate increase of 8 beats/min (agreement range -8 to +14 beats/ min) and a fivefold increase in VPB/h(agreement range -141 to +151) were obser ved after withdrawing therapy. Repetitive ventricular arrhythmias and ST changes were also more frequent off therapy but intra patient reproducibility was poor : kappa 0.12(95%confidence interval(CI)-0.01 to 0.25) for arrhythmias, -0.02( 95%CI-0.46 to 0.39) for ST depression and -0.01(95%CI-0.66 to 0.64) for ST elevation. Conclusions: The withdrawal of therapy is well tolerated soon after u ncomplicated MI; however, a generic but not individual risk of ventricular arrhy thmias and/or transient myocardial ischemia has to be taken into account.

中医药临床试验中的残余效应研究

残余效应是指前一次干预措施效应遗留时间超过两次干预时间间隔的一种效应遗留现象。在交叉设计的临床试验中,残余效应会降低受试者基线数据的可比性、干扰干预的实际临床效果,降低试验结果准确性。中医药临床试验中,干预措施的复杂性进一步加大了残余效应的处理难度,目前尚无针对性的全面处理方案。针对此难点问题,从残余效应的影响因素、问题根源、难点问题出发,对中医药临床试验中药物成分残余、治疗效应残余和心理效应残余三类残余效应的处理,展开深入分析并提出全面处理方案:通常设立洗脱期处理残余效应,并采用基线测量法验证残余效应处理效果;针对心理效应残余的特殊性,采用盲法结合洗脱期,并利用提问受试者的方式验证心理效应残余的处理效果;当试验无法使用洗脱处理或处理后仍存在残余效应时,采用混合效应模型处理试验数据解决残余效应。研究旨在为临床试验研究者处理残余效应提供参考,以完善试验设计方案,提高试验结果的准确性。

复方血栓通胶囊对糖尿病肾病Ⅲ期的临床研究

糖尿病肾病（DN）是糖尿病慢性并发症中常见的微血管病变,是引起糖尿病患者死亡的主要原因之一。DN一旦进入大量蛋白尿期将很难逆转,如何有效控制早期DN是目前亟待解决的问题。西医主要通过控制血压、血糖等,治疗有限。中医认为DN的临床表现以气阴两虚、血瘀脉络为主,病机特点为本虚标实,虚实夹杂,脾、肾、肝及气血阴阳之虚为本,气滞、湿阻、血瘀为标[1]。

一项关于回肠胆汁酸转运体抑制剂GSK2330672对原发性胆汁性胆管炎瘙痒症状影响的Ⅱa期随机、双盲、安慰剂对照、交叉研究

【据《Lancet》2017年2月报道】题：一项关于回肠胆汁酸转运体抑制剂GSK2330672对原发性胆汁性胆管炎瘙痒症状影响的Ⅱa期随机、双盲、安慰剂对照、交叉研究（作者Vinod SH等）高达70%的原发性胆汁性胆管炎（PBC）患者在病程中会出现瘙痒症状,而对其治疗又非常困难,熊去氧胆酸（UDCA）是治疗PBC的标准一线药物,但对瘙痒无效,因此临床上迫切需要新的治疗方法。回肠胆汁酸转运体（IBAT）抑制剂可阻断胆汁酸肠肝循环,但目前尚无临床研究评估其对PBC瘙痒症的影响。

单病例随机对照试验的周期设计在中医药临床疗效评价中的应用研究

目的：在中医药临床试验设计中,对单病例随机对照试验（N-of-1）的导入期与洗脱期的设置做进一步说明。方法：运用比较分析的方法,参考2010版CONSORT指南、2015最新版CENT指南以及收集、整理、阅读国内外相关文献。结果：单病例随机对照试验有必要设置合理的导入期与洗脱期,在中医药临床研究领域中应根据具体的干预措施、目标疾病的特点以及患者意愿设置个性化的导入期与洗脱期。结论：单病例随机对照试验符合中医个体化诊疗的特点,是对中医药临床疗效评价体系的补充。由于中医药临床干预具有复杂性,中药复方在体内的代谢机制尚不清楚,在此形势下规范中医药临床试验设计从而获得更加符合临床实际的试验证据就显得尤为必要。

自体血清滴眼液治疗严重干眼症的疗效:前瞻性随机病例对照研究

Purpose: To evaluate the effectiveness of the autologous serum eyedrops in the treatment of severe dry eye patients. Design: Prospective randomized case- control study. Methods: Thirty- seven eyes of twenty severe dry eye patients without punctal occlusion were enrolled in this study. After 2 weeks of washout, they were randomly assigned to two groups. Group A patients used only preservative- free artificial tears, and group S patients used only autologous serum eyedrops. We evaluated the results of Schirmer test, fluorescein and rose bengal staining scores, tear film breakup time (BUT), and subjective symptom scores before and 2 weeks after treatment. Results: Mean BUT and fluorescein and rose bengal staining scores, as well as subjective symptom scores, showed significant improvement in the patients assigned to autologous serum eyedrops compared with subjects assigned to preservative- free artificial tears after 2 weeks of treatment. Conclusions: Autologous serum eyedrops were found effective in the treatment of severe dry eye disease, as evidenced by improvement of tear stability and ocular surface vital staining scores.

发散式冲击波治疗陈旧性踝关节扭伤38例临床观察

踝关节扭伤临床极为常见,可发生于任何年龄。多因在外力作用下,通常在下坡、行走、跑步、跳跃或下楼梯时,踝跖屈曲,突然向外翻或向内翻,外、内侧副韧带受到强大的张力作用,致踝关节失去平衡,发生扭伤。

昔多芬可以提高绝经前1型糖尿病合并性唤起障碍患者的性功能:一项双盲、交叉、安慰剂对照的预试验

Objective: To verify whether sildenafil is effective in type 1 premenopausal women affected by sexual arousal disorder (SAD). Design: Double-blind, crossover, placebo-contro-lled study. Setting: Gynecological diabetic outpatient clinic and sexual clinic. Patient(s): Thirty-six type 1 premenopausal diabetic women affected by SAD. Intervention(s): Two 8-week periods of sildenafil 100 mg, washout, and placebo, by two possible sequences. Main Outcomes Measure(s): Each woman submitted blood samples to measure HbA 1c, and T, free T (FT), and PRL. Efficacy was assessed [1] subjectively by the Personal Experiences Questionnaire based on the 5- point Likert scale, quantifying arousal, desire, orgasm, enjoyment of sexual activities, and frequency of sexual relationships; and [2] objectively by translabial color Doppler ultrasound to measure the resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end diastolic velocity of clitoral arteries. Result(s): Thirty-two women completed the study. The mean HbA 1c value was 8.0% ± 1.8% , and plasma concentrations of T, FT, and PRL were normal. Sildenafil seems to improve arousal, orgasm and sexual enjoyment, and dyspareunia in women affected by type 1 diabetes. However, by flowmetric measurements, the mean RI was significantly lower and both the mean PI and PSV of the clitoral arteries were significantly higher compared with baseline and placebo. Conclusion(s): Sildenafil seems to improve subjective sexual aspects and can be used to treat objectively genital arousal disorder of premenopausal women with type 1 diabetes.

局部长期应用β阻滞剂治疗的健康个体中的支气管反应性研究

Objective: To assess the impact of long-term treatment with topical timolol on bronchial reactivity in healthy individuals. Methods: Twenty-one other wise healthy individuals with high-pressure primary open-angle glaucoma were enrolled in a randomized controlled clinical trial. Eleven patients underwent 3 years of topical 0.5% timolol treatment followed by a 1- year washout period; 10 patients underwent primary argon laser trabeculoplasty. Functional variables and bronchial reactivity (forced expiratory volume in 1 second and metacholine challenge test results) were assessed in both groups at enrollment and after 3 and 4 years of follow-up. Results: After 3 years, a measurable response to metacholine challenge was recorded in 6 of 11 otherwise symptom-free individuals treated with 0.5% timolol twice daily. A detectable response to metacholine challenge was still present in half of these individuals (3 of 6) when further washed out for 1 year from the topical β-blocker. No significant variation in bronchial reactivity was measured in the laser-treated group during 4 years of follow-up. Conclusions: Healthy individuals who undergo long-term topical application of a nonselective β-blocker (0.5% timolol) can develop a subclinical increase in bronchial reactivity. This phenomenon may not be completely reversible on withdrawal of the β-blocker.

不含防腐剂的非选择性β受体阻滞剂治疗青光眼及高眼压症时泪液中白介素-1β的浓度

To evaluate the ocular surface inflammatory response to the presence of preservatives in nonselective beta-blocker eyedrops. Prospective, crossover, single-masked, randomized clinical study. study population: Twenty primary open-an-gle glaucoma or ocular hypertensive patients were divided in two groups, one treated with preservative-free timolol 0.5% (group 1) and the other with preserved timolol 0.5% (group 2) eyedrops. After 60 days of therapy and 3 more weeks of washout, the two groups switched to the other therapy. procedure: At each visit, basal tear samples were collected from the inferior conjunctival fornix for the determination of interleukin (IL)-1β tear concentrations by an enzyme-linked immunosorbent assay. Intraocular pressure measurement, conjunctival hyperemia, superficial punctate keratitis, and tear film breakup time were evaluated. main outcome measure: IL-1β concentration in tears following the use of preserved eyedrops. IL-1β tear concentrations increased significantly in both groups,compared with baseline values, during preserved timolol therapy. There were no statistically significant changes in hyperemia and superficial punctate keratitis throughout the study in either group. A statistically significant breakup time reduction was observed in both groups after 30 days and after 60 days of preserved therapy. The use of preservatives in timolol 0.5% eyedrops leads to tear film instability and ocular surface inflammatory changes documented by a reduction of breakup time and an increase of IL-1β tear concentrations. Preservative-free betablockers are preferable for long-term hypotensive therapy to prevent ocular surface inflammation.

麦考酚酸吗啉乙酯和环孢素治疗中重度慢性斑块型银屑病的系列研究

Background:There are numerous studies that individually evaluate the efficacy/effectiveness and toxicity of drugs in the systemic treatment of psoriasis.On the contrary,we can hardly find studies that compare each other.Objective:To evaluate and compare the effectiveness and toxicity of mycophenolate mofetil and cyclosporin in chronic plaque psoriasis through a prospective,sequential,cross-over,non-randomized,two phase,open-label study.Patients/Methods:Eight patients(five women and three men;mean age 57,range 35-78)with moderate-to-severe chronic plaque psoriasis were included in the study.They were treated with oral mycophenolate mofetil(30 mg/kg/day)over a period of 16 weeks.Following a variable wash out period and after a new outbreak of the disease,oral cyclosporinwas introduced at a dose of 4 mg/kg/day.During both treatment regimens,follow-up visits were performed at 3,8 and 16 weeks.Results:In both groups,the PASI started to decrease once treatment was begun.Cyclosporin was faster and statistically a lot more effective than mycophenolate mofetil,reaching a higher number of complete remissions and better percentages of PASI improvement from baseline(45.7%,60.2%and 60.5%at 3,8 and 16 weeks respectively for mycophenolate mofetil,and 89.7%,95.3%and 95.3%respectively at the same intervals for cyclosporin).Cyclosporin was also more predictable in its action as the percentage of improvement along the follow up visits had a much wider range for mycophenolate mofetil.Overall,the tolerability of both drugs was good.None of the patients had to discontinue treatment because of an adverse event.Two patients treated with cyclosporin showed increased plasma levels of creatinine.Conclusions:Cyclosporin is more effective,fast,and predictable in its effect than mycophenolatemofetil to control moderate-to-severe chronic plaque psoriasis.Both drugs are well tolerated in short courses of treatment.

Kukui果油外用治疗银屑病的效果

Background: No cure for psoriasis exists for the 1-3%of the American population who suffer from it; however, anecdotal reports from patients with psoriasis visiting Hawaii who purchased kukui nut oil, claim it helped reduce the severity of their lesions. Objective: This pilot study was a double-blind, placebo-controlled clinical trial to determine the effectiveness of kukui nut oil as a topical treatment for psoriasis. Methods: Thirty adult subjects (18-78 year) were recruited from the community for a 12-week randomized, double-blind, placebocontrolled pilot study. Subjectswere previously diagnosedwith mild, stable plaque psoriasis (less than 15%of total body surface area [TBSA]) and agreed to abstain from other treatments during the course of the study. Following a 4-week washout period the subjects were randomized into a treatment group (15 subjects applying kukui nut oil) or a control group (15 applying the mineral oil placebo). Patients were seen every 2 weeks (seven visits at 0, 2, 4, 6, 8, 10, and 12 weeks) by a dermatological nurse practitioner under the general supervision of a board certified dermatologist. Measurable outcomes included evaluation of one targeted lesion and of the overall severity of their, psoriasis using clinical evaluation, Psoriasis Area and Sensitivity Index (PASI), Global Severity of Psoriasis Scale, and photographs. Each patient also evaluated their own lesions daily using the Global Severity of Psoriasis Scale, and noted any side-effects or other treatments used. Results: Although both groups improved, we found no significant difference between the treatment (kukui nut oil) and the placebo (mineral oil) among the 24 out of 30 subjects (80%) who completed the study. No side-effects or adverse events were reported. Conclusion: Kukui nut oil did not significantly reduce symptoms of psoriasis; however, this was a small pilot study, and the use of this oil cannot be dismissed without using a larger study population of patients with psoriasis.

无证据显示稳定型心脏病患者突然短期停用他汀类药物会增加急性冠状动脉综合征的发生

Background-For a variety of reasons, many patients abruptly discontinue statin therapy. The present analysis was conducted to determine whether the risk of cardiovascular outcomes increases after withdrawal of statin therapy in a stable cardiac population. Methods and Results-In the Treating to New Target(TNT) study, 2 doses of atorvastatin (10 and 80 mg once daily) are being used in a double-blind parallel-group design. Of the 18 468 patients screened for study participation, 16 619 entered a dietary lead-in/drug-washout period, and of these, 15 432 eligible participants began treatment with atorvastatin 10 mg/d on an open-label basis. Of the subjects who entered the dietary lead-in/drug-washout period, 57%were receiving prior statin therapy. During the 6-week drug-washout period, there were 24 primary events(defined as coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke); throughout the subsequent 8-week open-label period, there were 31 primary events. This equated to monthly Kaplan-Meier event rates of 0.20%during washout and 0.26%in the open-label phase. Event rates were therefore similar during the 2 phases. Conclusions-The present analysis demonstrates that short-term discontinuation of statin therapy in stable cardiac patients apparently does not lead to a clinically important increased risk of acute coronary syndromes.

拉坦前列素-噻吗心安联合用药与单用拉坦前列素24h眼压控制效果比较

Objective: To evaluate the 24- hour efficacy and safety of the latanoprost-timolol maleate-fixed combination vs latanoprost therapy in patients with primary open-angle glaucoma. Methods: A prospective, observer-masked, crossover, activecontrolled, randomized comparison in which after a 6- week medicine-free period, patients were randomized to either latanoprost-timolol-fixed combination therapy or latanoprost therapy, both dosed once each evening, alone for 8 weeks. Patients were then switched to the opposite treatment for 8 weeks. At the end of the washout and treatment periods, a 24- hour diurnal curve was performed. Results: The baseline untreated mean± SD diurnal curve in 37 patients who completed the study was 24.2± 2.0 mm Hg. The mean diurnal curve was 19.2± 2.6 mm Hg for those who received latanoprost therapy alone and 16.7 ± 2.1 mm Hg for those who received the fixed combination therapy (P<.001). The fixed combination therapy also provided a lower absolute intraocular pressure level (1.5- 2.9 mm Hg, P<.001) and a greater intraocular pressure reduction from the untreated baseline (P<.001). Stinging was statistically lower with latanoprost therapy alone (P=.04), but itching was statistically increased compared with the fixed combination therapy (P=.04). Conclusion: The result of this study suggests that the latanoprost-timolol-fixed combination compared with latanoprost therapy alone provides improved intraocular pressure reduction over the 24- hour diurnal curve and for each individual time point in patients with primary open-angle glaucoma.

“赛外良药,赛内禁药”——糖皮质激素

简要介绍糖皮质激素的化学结构及药理作用、在《禁用清单》中的分类及主要变化、运动员如何避免误服误用等,帮助运动员及辅助人员深入了解糖皮质激素的药理作用和相关禁用规定,在需要时合理用药,规避误服风险。

吲哒帕胺抗高血压疗效及安全性观察

94例患者经过2周安慰剂洗脱期后,48例服吲哒帕胺缓释片1.5mg,46例服吲哒帕胺普通片2.5mg,每日1次,均服药6周。结果:两组治疗后2、4、6、8周血压较治疗前明显降低(P【0.01),8周末两组降压总有效率分别为70.8％及73.9％(P】0.05)。吲哒帕胺缓释片组不良反应(2％)

NESTOR研究:缓释型吲达帕胺和依那普利减少高血压合并2型糖尿病患者微蛋白尿的疗效相同

Objectives: To test whether microalbuminuria in patients with type 2 di abetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system <<the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril>> in reducing microal buminuria. Design: A multinational, multicentre, controlled, double-blind, doub le-dummy, randomized, two-parallel-groups study over 1 year. Methods: After a 4-week placebo run-in period, 570 patients (ages 60.0 ±9.9 years, 64%men) w ith type 2 diabetes, essential hypertension <<systolic blood pressure (SBP) 140- 180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg>>, and persistent microal buminuria (20-200 μg/min) were allocated randomly to groups to receive indapam ide SR 1.5 mg (n=284) or enalapril 10 mg (n=286) once a day. Amlodipine, atenolo l, or both were added, if necessary, to achieve the target blood pressure of 140 /85 mmHg. Results: There was a significant reduction in the urinary albumin: cre atinine ratio. Mean reductions were 35%<<95%confidence interval (CI) 24 to 43>> and 39%(95%CI 30 to 47%) in the indapamide SR and enalapril groups, respectiv ely. Equivalence was demonstrated between the two groups <<1.08 (95%CI 0.89 to 1 .31%); P=0.01>>. The reductions in mean arterial pressure (MAP) were 16.6 ±9.0 mmHg for the indapamide SR group and 15.0 ±9.1 mmHg for the enalapril group (NS ); the reduction in SBP was significantly greater (P =0.0245) with indapamide SR . More than 50%of patients in each group required additional antihypertensive t herapy, with no differences between groups. Both treatments were well tolerated. Conclusions: Indapamide-SR-based therapy is equivalent to enalapril-based th erapy in reducing microalbuminuria with effective blood pressure reduction in pa tients with hypertension and type 2 diabetes.