Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial.

OBJECTIVE: To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors. DESIGN: Randomised controlled trial. SETTING: District general hospital in North London. SUBJECTS: 148 inpatients requiring start of warfarin treatment. INTERVENTIONS: Management by trainee doctors (to achieve therapeutic range of international normalised ratio of 2 to 3) with indirect assistance from computerised decision support system (intervention group) or without such assistance (control group). MAIN OUTCOME MEASURES: Median time to therapeutic range, stable dose, and first pseudoevent (excessive international normalised ratio after therapeutic range has been reached) and person time spent in the therapeutic range. RESULTS: 72 patients were randomised to the intervention group and 76 to control group. Median time to reach international normalised ratio of > or = 2 was not significantly different in the two groups (3 days). Median time to achieve a stable dose was significantly lower in intervention group than in controls (7 days v 9 days, P = 0.01) without excessive overtreatment or undertreatment with anticoagulant. Patients in intervention group spent greater proportion of time in therapeutic range, both as inpatients (59% v 52%) and outpatients (64% v 51%). CONCLUSION: The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors.     

Influencing the fibrinolytic activity by antithrombotics in patients with atherosclerosis

In 106 atherosclerotic patients receiving an anticoagulant therapy and 91 patients receiving acetylsalicylic acid, fibrinogen and fibrin degradation products were determined as well as euglobulin lysis before and after venous occlusion. Platelet function data and thromboxane (TXB2) were also determined. Since "moderate" anticoagulant therapy with thromboplastin time values 26-40% results in deteriorated fibrinolysis data, anticoagulant therapy is strictly to remain within the therapeutic range of 15-20% up to 25% thromboplastin time at maximum. Treatment with acetylsalicylic acid proved useful on condition that the required dose was determined individually. This type of treatment will then be able to reduce the thromboxane level and positively influence the fibrinolytic potential.     

Sex Differences in Treatment Quality of Self-Managed Oral Anticoagulant Therapy: 6,900 Patient-Years of Follow-Up

Background

Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists has demonstrated efficacy in randomized, controlled trials. However, the effectiveness and efficacy of PSM in clinical practice and whether outcomes are different for females and males has been sparsely investigated.The objective is to evaluate the sex-dependent effectiveness of PSM of oral anticoagulant therapy in everyday clinical practice.

Methods

All patients performing PSM affiliated to Aarhus University Hospital and Aalborg University Hospital, Denmark in the period 1996–2012 were included in a case-series study. The effectiveness was estimated using the following parameters: stroke, systemic embolism, major bleeding, intracranial bleeding, gastrointestinal bleeding, death and time spent in the therapeutic international normalized ratio (INR) target range. Prospectively registered patient data were obtained from two databases in the two hospitals. Cross-linkage between the databases and national registries provided detailed information on the incidence of death, bleeding and thromboembolism on an individual level.

Results

A total of 2068 patients were included, representing 6,900 patient-years in total. Males achieved a significantly better therapeutic INR control than females; females spent 71.1% of the time within therapeutic INR target range, whereas males spent 76.4% (p<0.0001). Importantly, death, bleeding and thromboembolism were not significantly different between females and males.

Conclusions

Among patients treated with self-managed oral anticoagulant therapy, males achieve a higher effectiveness than females in terms of time spent in therapeutic INR range, but the incidence of major complications is low and similar in both sexes.     

Reversibility of the effects of chronic paternal exposure to cyclophosphamide on pregnancy outcome in rats

Low-dose chronic treatment of the male rat with the antitumor drug cyclophosphamide causes a time- and dose-dependent increase in pre- and post-implantation loss in the untreated females to which he is mated. The objective of the present study was to determine whether such effects are reversed, and if so at what time after cessation of drug treatment. Adult male Sprague-Dawley rats were gavage fed daily, 6 times per week for 9 weeks, with saline (control) or with 1 of 3 doses of cyclophosphamide, 1.4, 3.4 or 5.1 mg/kg/day. After the 9 weeks of treatment and at 2-week intervals thereafter, each male was mated with 2 females in proestrus. The females were caesarian sectioned 20 days later and pregnancy outcome assessed. After 9 weeks of drug treatment, pre-implantation loss increased more than 3-fold from 6% in the control group to 21% in the 5.1 mg/kg/day cyclophosphamide treatment group. Post-implantation loss increased in a dose dependent fashion from 5% in the control group to 74% in the 5.1 mg/kg/day cyclosphosphamide treatment group. Pre-implantation loss rapidly decreased upon cessation of treatment with cyclophosphamide: within 2 weeks it had returned to within the control range. Within just 2 weeks after termination of drug treatment in the 5.1 mg/kg/day cyclophosphamide treatment group, post-implantation loss decreased by half to 44%; it had decreased to 11% by 4 weeks and then was maintained at 4-6% thereafter. In the 3.4 mg/kg/day cyclophosphamide treatment group, post-implantation loss returned to the control range by 4 weeks. Thus, the effects of paternally administered cyclophosphamide on progeny outcome are reversible. The timing of reversal suggests that the effects on pre-implantation loss are due to a drug effect on spermatozoa either in the epididymis or near the time of spermiation while those on post-implantation loss are due to an additional effect on spermatids in the seminiferous tubules.     

Long-term Anticoagulant Therapy after Myocardial Infarction in Women

A multicentre trial from five medical departments in Oslo has been carried out to determine the value in women patients of one year''s long-term anticoagulant therapy. Follow-up long-term laboratory control and anticoagulant dosage were performed at one centre (the Rikshospitalet). One hundred and fifty-nine patients were assigned randomly into two similar well-matched groups (control and treatment). Dosage was controlled by Thrombotest, aiming at 10–20% levels, and 50% of the tests were less than 14%. Compared with the control group, the treatment group showed a significant reduction in mortality and in reinfarction rate. No serious bleeding complications occurred. It is concluded that women benefit as much as men from long-term anticoagulant therapy.     

Cyclosporin treatment of IgA nephropathy: a short term controlled trial.

Cyclosporin''s known regulatory effects on the immune system suggest that it may be useful in treating patients with IgA nephropathy. A randomised prospective single blind study of 19 patients with IgA nephropathy and proteinuria (greater than 1.5 g/day) was conducted to determine the therapeutic value of cyclosporin. The patients were divided into two groups: nine patients were given oral cyclosporin (5 mg/kg/day) for 12 weeks and 10 patients a placebo. The two groups were comparable in age of presentation, ratio of men to women, plasma creatinine and serum IgA concentrations, creatinine clearance, daily urinary protein excretion, severity of renal histopathological changes, and prevalence of hypertension. A significant reduction of proteinuria and an increase of plasma albumin concentration was observed with treatment with cyclosporin. Nevertheless, a significant rise of plasma creatinine concentration and a fall in creatinine clearance was found in patients after six weeks'' treatment with cyclosporin, although the plasma cyclosporin concentrations were maintained within a narrow therapeutic range. Serum IgA concentrations were reduced in seven patients. Renal function improved within eight weeks after treatment was stopped. Three months after treatment was stopped proteinuria remained less than half of the pretreatment values in three patients. No similar biochemical changes were observed in the controls. Short term cyclosporin therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. As transient renal impairment was seen, despite cyclosporin concentrations being maintained within a narrow therapeutic range, indiscriminate use of cyclosporin in glomerulonephritis should be discouraged.     

Computer control of anticoagulant dose for therapeutic management.

OBJECTIVE--To improve the standard of managing anticoagulant treatment and provide a basis for therapeutic quality control. DESIGN--Implementation of a comprehensive computerised system for decision support. SETTING--Three anticoagulation clinics in South Warwickshire. SUBJECTS--Patients in South Warwickshire receiving anticoagulant treatment from September 1988 to March 1989. MAIN OUTCOME MEASURE--International normalised ratio was measured and recorded at each visit. RESULTS--688 Patients'' visits were analysed statistically, and a 38% improvement was achieved in the results of international normalised ratios falling within the recommended therapeutic ranges of the British Society for Haematology. CONCLUSIONS--The implementation of a computerised anticoagulation support system resulted in better management of patients. The system provides a basis for uniform management of treatment and a common platform for national or international trials.     

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment ≥ 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician's global assessment was 4.4 ± 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (± 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.     

Implications of Using Different Methods to Characterise Anticoagulant Control in Patients with Second Generation Mechanical Heart Valve Prostheses

Objective

Characterisation of anticoagulant control is fundamental to investigations of its association with clinical outcome. Anticoagulant control depends on several factors. This paper aims to illustrate the implications of different methods for measuring and analysing anticoagulant control in patients with second generation mechanical heart valve prostheses.

Methods

International normalised ratio (INR) data collected during the 10-year follow-up of a randomised controlled trial were analysed. We considered the influence of: 3 different target INR ranges; anticoagulant control expressed as the proportion of INR readings (PoR) vs. anticoagulant control follow-up time (PoT); 3 ways of describing the profile of anticoagulant control over time.

Results

Different target INR ranges dramatically influenced derived measures of anticoagulant control; the PoT within the target range varied from 88% for the widest to 28% for narrowest range. Overall distributions of PoR and PoT observations were similar but differed by up to ±20% for individuals; PoT exceeded PoR when control was good but was less than PoR when control was poor. Classifying PoT outside the target range showed that widely varying combinations of PoT too high and too low are possible across individuals.

Conclusions

Researchers'' choices about methods for measuring and quantifying anticoagulant control markedly influence the values derived from INR readings. The use of different methods across studies makes it difficult or impossible to compare findings and to establish an evidence base for clinical practice. Methods for quantifying anticoagulant control should be standardised.     

咬合运动与注射醋酸泼尼松龙治疗滑膜炎的疗效比较

目的：比较咬合运动和关节下腔注射醋酸泼尼松龙治疗颞下颌关节滑膜炎的临床效果。方法：选择牙列完整、无第三磨牙阻生、符合颞下颌关节滑膜炎诊断标准的120例患者,随机分为实验组和对照组,每组60例。实验组行咬合运动,每次34个循环,每日3-4次,治疗周期为12个月;对照组给予醋酸泼尼松龙0．0125g＋0．5m12％利多卡因关节下腔注射一次,比较两种方法谛治爿效果。结果：实验组的60例患者均在治疗后1-2W疼痛消失,追踪3．12个月无复发。对照组的60例患者,2个周后有18。例无效,无效率为30％,两组比较其结果有显著性差异（P〈O．001）;3个月后有22例无效,无效率为36．67％,两组比较其结果有显著性差异（P〈0．001）。结论：咬合运动组的治疗效果显著高于醋酸泼尼松龙注射组,咬合运动能有效的治疗滑腱炎并减少患者的治疗痛苦。     

咬合运动与注射醋酸泼尼松龙治疗滑膜炎的疗效比较

目的:比较咬合运动和关节下腔注射醋酸泼尼松龙治疗颞下颌关节滑膜炎的临床效果。方法:选择牙列完整、无第三磨牙阻生、符合颞下颌关节滑膜炎诊断标准的120例患者,随机分为实验组和对照组,每组60例。实验组行咬合运动,每次3-4个循环,每日3-4次,治疗周期为12个月;对照组给予醋酸泼尼松龙0.0125g+0.5ml2%利多卡因关节下腔注射一次,比较两种方法的治疗效果。结果:实验组的60例患者均在治疗后1-2w疼痛消失,追踪3-12个月无复发。对照组的60例患者,2个周后有18例无效,无效率为30%,两组比较其结果有显著性差异(P<0.001);3个月后有22例无效,无效率为36.67%,两组比较其结果有显著性差异(P<0.001)。结论:咬合运动组的治疗效果显著高于醋酸泼尼松龙注射组,咬合运动能有效的治疗滑膜炎并减少患者的治疗痛苦。     

Interaction between anticoagulants and contraceptives: an unsuspected finding.

To assess the effects of oral contraceptives on anticoagulant treatment the prothrombin times of 12 patients were measured while they were taking both drugs simultaneously and while they were taking only anticoagulants. The mean prothrombin time ratio was significantly higher when patients were taking both drugs than when they were taking only anticoagulants and their doses of anticoagulant were significantly lower. During both periods most of the prothrombin values remained in the therapeutic range. These findings suggest that, contrary to the common belief that oral contraceptives diminish the effects of anticoagulants, contraceptives in fact potentiate the action of the anticoagulants.     

脑益嗪、非那根联合治疗耳石症疗效及复发率影响

摘要 目的：探究耳石症应用脑益嗪与非那根联合治疗的有效性,并就联合治疗对复发率影响进行分析。方法：选择2018年1月至2019年1月于我院接受治疗的98例耳石症患者,按照随机数字表法将其均分为研究组与对照组（每组各49例）,对照组单纯接受非那根治疗,研究组在对照组基础上加用脑益嗪进行治疗,两组治疗时间均为4 w,对比两组治疗有效率,对比治疗前、治疗第2 w研究组及治疗第4 w时两组的眩晕评定量表（Dizziness Handicap Inventory,DHI）评分,对比两组治疗后1 w平均眩晕次数及平均眩晕时间,最后对两组实施为期3个月的随访,记录其耳石症复发率并进行对比。结果：（1）研究组治疗有效率显著高于对照组（97.96 % vs. 81.63 %,P<0.05）;（2）治疗前两组DHI评分对比差异不具有统计学意义（P>0.05）,治疗后第2 w及第4 w研究组DHI评分均低于对照组（P<0.05）;（3）治疗后1 w内研究组平均眩晕次数及平均眩晕时间均低于对照组（P<0.05）;（4）随访显示研究组治疗后3个月内复发率显著低于对照组（4.08 % vs. 16.33 %,P<0.05）。结论：脑益嗪联合非那根对耳石症具有较好的治疗效果,能够显著改善患者眩晕症状,同时治疗后复发率更低。     

乳杆菌活菌胶囊联合甲硝唑栓治疗细菌性阴道病的疗效及预防复发作用

目的探讨乳杆菌活菌胶囊联合甲硝唑栓治疗细菌性阴道病的疗效及预防复发作用。方法将88例细菌性阴道病患者的随机分为观察组和对照组。观察组患者予以乳杆菌活菌胶囊和甲硝唑栓联合治疗,对照组患者予以单纯的甲硝唑栓治疗。乳杆菌活菌胶囊阴道放置,每次1粒,每晚1次,连用10d。甲硝唑栓阴道放置,阴道放置,每次1粒,每晚1次,连用10d。两组患者治疗期间及复查前禁止性生活,避免冲洗阴道及使用抗生素和微生态制剂。观察两组患者治疗停药后2周的临床疗效,并比较随访3个月及6个月内的复发率。结果治疗停药后2周,观察组的临床总有效率为95．45％,明显高于对照组的81．82％（χ2=4．06,P〈0．05）。治疗后进行随访,观察组的3个月及6个月内复发率分别为7．14％和16．67％,均明显低于对照组的25．00％和38．89％（χ2=4．75和4．87,P〈0．05）。结论乳杆菌活菌胶囊联合甲硝唑栓治疗细菌性阴道病具有较好的疗效,并降低其复发率,具有治疗与预防细菌性阴道病的双重作用。     

吉西他滨联合奥沙利铂对晚期胰腺癌合并肝转移的临床疗效观察

目的:探讨吉西他滨联合奥沙利铂对晚期胰腺癌合并肝转移的临床疗效及其安全性。方法:回顾性研究84例晚期胰腺癌伴有肝转移的患者,根据化疗方案分为实验组和对照组,每组42例,实验组给予吉西他滨联合奥沙利铂化疗(GEMOX方案),对照组给予5-FU化疗,治疗4周后,比较两组临床受益率、治疗有效率、无疾病进展生存期、1年生存率和不良反应的发生情况。结果:当转移癌体积小于肝体积75%时,对照组的临床受益率为6.06%,有效率为12.12%,而实验组的临床受益率为32.26%,有效率为58.06%,与对照组的患者相比均显著升高(P<0.05)。实验组中位无疾病进展生存期为18个周,21%的患者2年内达到无疾病进展,患者的平均生存期为37个周,在1年生存率为35%;而对照组中,中位无疾病进展生存期为9个周,1年生存率为0,实验组1年生存率显著高于对照组者(P<0.05)。两组不良反应发生情况无明显差别。结论:吉西他滨联合奥沙利铂治疗晚期胰腺癌合并肝转移的疗效优于以5-FU为主的化疗,且二组相比不良反应无明显差别,值得临床进一步研究。     

Effectiveness of Gemzar-Cisplatin therapy in stage IIIA-N2, IIIB and IV non-small cell lung cancer

120 chemotherapy naive patients were treated with gemcitabine 1250 mg/m2 iv. days 1 and 8 and cisplatin 70 mg/m2 iv. on day 1 between May 1999 and June 2001. The treatments were administered in 21 cycles. The median age of the patients was 53.1 years, the male/female ratio 65%-35%. Performance status was: WHO 0: 26%, WHO 1: 74%. The staging of patients were: IIIA-N2 23%, IIIB 37%, IV 40%. By histology the tumors were: 53.3% adenocarcinoma, 40% squamous cell carcinoma, 2.5% adenosquamous carcinoma, 0.8% macrocellular carcinoma and 3% non-small cell carcinoma (not categorised). We evaluated 413 cycles of chemotherapy. The median number of cycles was 3.44. The primary endpoint of the study was the median survival and time to progression, and the response rate. The results are the following: RR 40% (PR 37.5%, CR 2.5%), MR 13.3%, SD 25%, PD 22%. The time to progression (TTP) in the SD+MR group: 29.8 weeks, in the RR group: 34.1 weeks, mean of all patients: 28.1 weeks. The survival time was estimated by Kaplan-Meier curves. The median survival (MS) of all treated patients was: 54.9 weeks, in the PD group: 34.4 weeks, in the SD+MR group: 59.1 weeks, in the PR+CR group: 62.1 weeks. Conclusion: gemcitabine and cisplatin combination is a very well tolerated therapeutic regimen in the 1st line treatment of NSCLC. Furthermore, this treatment improves the RR and the survival of the patients as well.     

丽珠肠乐与肝泰乐对照治疗慢性肝炎的研究

本文报告用丽珠肠乐与肝泰乐对照治疗慢性肝炎６０例,其中治疗组３０例,对照组３０例。两组基础治疗相同,对照组用肝泰乐,肌苷片,复合维生素Ｂ。结果,治疗组显效２１例,有效５例,无效４例。对照组显效１３例,有效５例,无效１２例。经统计学处理、治疗组有效率明显高于对照组（Ｐ＜０．０５）,治疗组在治疗前后血内毒素有明显下降。     

稳心颗粒治疗高血压性心脏病心律失常的疗效分析

目的:探讨稳心颗粒治疗高血压心脏病合并心律失常中的效果,为患者提供更好的治疗方案。方法:将110例高血压性心脏病合并心律失常患者随机分成对照组和治疗组,每组各55例。两组均进行常规的降压治疗,其中治疗组在常规治疗的基础上服用稳心颗粒,1袋/次,3次/d,6周为一个疗程。对比两组治疗效果。结果:治疗后,治疗组总有效率为89.1%(49/55)显著高于对照组的72.7%(40/55),差异具有统计学意义(P0.05);治疗组患者阵发性和永久性心房颤动占比分别5.5%(3/55)、0,低于对照组的12.7%(7/55),1.8%(1/55),其中阵发性心房颤动比较差异有统计学意义(P0.05);两组患者均未出现较明显的不良反应。结论:稳心颗粒治疗高血压心脏病合并心律失常中疗效确切,不良反应少。     

Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin—A Nationwide Cohort Study

Aim

Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy.

Methods and Results

Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456), and 63% in the warfarin group (n = 774). Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5) and 6.9 (IQR 3.9 to 12.1) weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1) in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42). Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08).

Conclusion

Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.     

萘替芬酮康唑乳膏治疗股癣疗效观察

目的观察萘替芬酮康唑乳膏治疗股癣疗效和安全性。方法将160例患者随机分为治疗组和对照组,治疗组外用萘替芬酮康唑乳膏;对照组外用硝酸咪康唑乳膏,均早晚各涂一次。用药2周及停药3周后分别进行临床疗效和真菌学疗效评价。结果治疗2周时治疗组有效率为92.50%,而对照组有效率为76.25%,两组间差异有统计学意义(P<0.05)。治疗2周时真菌清除率治疗组97.50%,对照组87.50%,两组间差异有统计学意义(P<0.05)。停药3周时治疗组有效率为96.25%,对照组有效率为75.00%,两组间差异有统计学意义(P<0.05)。停药3周时真菌学清除率治疗组97.50%,对照组85.00%,两组间差异有统计学意义(P<0.05)。无明显不良反应发生。结论萘替芬酮康唑乳膏治疗股癣安全有效。