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COPD钟南山柳叶刀英文版--羟甲司坦对AECOPD的作用(PEAC研究)

COPD钟南山柳叶刀英文版--羟甲司坦对AECOPD的作用(PEAC研究)
COPD钟南山柳叶刀英文版--羟甲司坦对AECOPD的作用(PEAC研究)

E?ect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study

Jin-Ping Zheng, Jian Kang, Shao-Guang Huang, Ping Chen, Wan-Zen Yao, Lan Yang, Chun-Xue Bai, Chang-Zheng Wang, Chen Wang,

Bao-Yuan Chen, Yi Shi, Chun-Tao Liu, Ping Chen*, Qiang Li, Zhen-Shan Wang, Yi-Jiang Huang, Zhi-Yang Luo, Fei-Peng Chen, Jian-Zhang Yuan, Ben-Tong Yuan, Hui-Ping Qian, Rong-Chang Zhi, Nan-Shan Zhong

Summary

Background Chronic obstructive pulmonary disease (COPD) is characterised by air? ow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway in? ammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-in?ammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD.

Methods We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume

in 1 s (FEV

1) to forced vital capacity (FVC) ratio (FEV

1

/FVC) of less than 0·7 and an FEV

1

between 25% and 79% of the

predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin. ac.jp/ctr/index/htm) number UMIN-CRT C000000233.

Findings 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined signi? cantly in the carbocisteine group compared with the placebo group (1·01 [SE 0·06] vs1·35 [SE 0·06]), risk ratio 0·75 (95% CI 0·62–0·92, p=0·004). Non-signi? cant interactions were found between the preventive e? ects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated.

Interpretation Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.

Funding Kyorin Pharmaceuticals.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterised by air?ow limitation, and patho-physiologically involves many components including mucus hypersecretion, oxidative stress, and in? ammation in the airway and lungs.1 Therefore, agents active with mucolytic, anti-in?ammatory, and antioxidative e? ects could o? er promise for treatment.

In Europe and Asia, mucolytics such as carbocisteine have been widely used for treatment of respiratory diseases with phlegm production2 because of their capacity to facilitate sputum elimination.3,4 Furthermore, carbocisteine seems likely to have a role in antioxidation5,6 and anti-in? ammation7–9 that might be more important than mucolysis itself for long-term management of COPD. Clinical studies have shown bene?ts in preventing exacerbation of COPD with carbocisteine.10–12 H owever, these results have been inconclusive because of certain pitfalls in study design, such as small sample size, not being double-blinded, lack of placebo control, or short period of study.13 Poole and Black14 did a systematic review of mucolytics in COPD, which has been updated15 with

inclusion of the BRONCUS study16 using N-acetylcysteine.

Their results showed that mucolytics including carbo-

cisteine were e? ective in reducing the number of exacer-

bations in COPD and improving health status in all studies

except BRONCUS.16 Since evidence on long-term e? cacy

remains insu? cient, mucolytics are not recom m ended for

regular treatment by guidelines such as that of the Global

Initiative for Chronic Obstructive Lung Disease (GOLD).1

Clinical trials that closely follow reliable research study

designs are therefore warranted to clarify whether COPD

patients can bene? t from protracted mucolytic therapy.

The aim of this study was to assess the e? ectiveness in

preventing exacerbation, improving quality of life, as well

as the safety pro? les of long-term (1-year) carbocisteine

administration in patients with COPD.

Methods

Patients

Participants were eligible for inclusion if they were

diagnosed as having COPD with a postbronchodilator

Lancet 2008; 371: 2013–18

See Comment page 1975

Guangzhou Institute of

Respiratory Disease,

First A? liated Hospital of

Guangzhou Medical College,

Guangzhou,

China (Prof J-P Zheng MD,

Prof N-S Zhong MD);

First A? liated Hospital of China

Medical University, Shenyang,

China (Prof J Kang MD); Ruijing

Hospital, Shanghai Jiao Tong

University Medical School,

Shanghai, China

(Prof S-G Huang MD); Shenyang

PLA General Hospital, Shenyang,

China (P Chen MD); Peking

University Third Hospital,

Beijing, China (Prof W-Z Y ao MD);

First A? liated Hospital, Xi’An

Jiao Tong University, Xi’An, China

(Prof L Y ang MD); Zhongshan

Hospital, Fudan University,

Shanghai, China

(Prof C-X Bai MD); Xin Qiao

Hospital, Chongqing, China

(Prof C-Z Wang MD); Chao Y ang

Hospital, Beijing, China

(Prof C Wang MD); Tianjin General

Hospital, Tianjin, China

(B-Y Chen MD); Nanjing PLA

General Hospital, Nanjing, China

(Y Shi MD); Huaxi Hospital,

Chengdu, China (C-T Liu MD);

Second Xiangya Hospital,

Changsha, China

(*Prof P Chen MD); Changhai

Hospital, Shanghai, China

(Q Li MD); Second A? liated

Hospital of Dalian Medical

University, Dalian, China

(Z-S Wang MD); Hainan Province

Hospital, Haikou, China

(Y-J Huang MD); First Municipal

Hospital, Foshan, China

(Z-Y Luo MD); Second A? liated

Hospital of Guangzhou Medical

College, Guangzhou, China

(F-P Chen MD); Red Cross

Hospital, Guangzhou, China

(J-Z Y uan MD); Second Municipal

Hospital, Shenzhen, China

(B-T Y uan MD); Xinhai Hospital,

Guangzhou, China (H-P Qian MD);

and Panyu Hospital, Guangzhou,

China (R-C Zhi MD)

forced expiratory volume in 1 s (FEV?) to forced vital

capacity (FVC) ratio (FEV?/FVC) of less than 0·70 and an FEV? between 25% and 79% of predicted value. The severity of COPD was de? ned in accordance with GOLD criteria.1

Patients had to be aged between 40 and 80 years,

have a history of at least two COPD exacerbations within the previous 2 years, yet have remained clinically stable for over 4 weeks before the study, and have good oral and writing skills. Smoking status was recorded and veri? ed by history; non-smokers were also included in the study.Patients were excluded if they had a history of physician-diagnosed asthma, non-COPD respiratory disorders, lung volume reduction surgery or transplantation, other conditions likely to interfere with the study, a requirement for long-term oxygen therapy (12 h or more per day) or pulmonary rehabilitation, evidence of alcohol or drug misuse, known or suspected hypersensitivity to the study medication or part of its ingredients, current use of oral corticosteroids, involvement in an investigational drug trial during the previous 12 weeks, or onset of an exacerbation requiring systemic or oral corticosteroid therapy or hospitalisation during the run-in period. Those with a history of severe glaucoma or severe heart, liver, and kidney diseases, or di? use bilateral bronchiectasis, and those in pregnancy or lactation were also excluded from the study.Participants were enrolled from 22 medical centres in China, of which 20 were academic hospital-based centres and two were community-based pulmonary clinics; six were located in northern China, four in eastern China, nine in southern China, and three in western China.The study was approved by local ethics committees and was done in compliance with the Declaration of H elsinki (1996). All patients gave written in-formed consent.

Study design

This was a multicentre, randomised, double-blind, placebo-controlled, parallel-group study. The study protocol was designed by an investigator steering committee and transplanted to all study sites thereafter. All investigators were trained before the trial to ensure reliable study quality, with special emphasis on understanding of the protocol, how to do a spirometry test, blinding of allocation, drug management, and compliance with good clinical practice. Beijing Contract Research Organisation (Beijing, China) was exclusively responsible for data management, data analysis, and data quality control.Randomisation was done using the predetermined computer-generated randomisation list provided by a statis-tician from the Beijing Contract Research Organisation. The processing of ran d om i sation was strati? ed by study centre, based on a block size of four, to allow for a balanced number of participants in both groups at a centre level. At each centre, the enrolled participants were allocated in order of their assigned numbers to the carbocisteine group or the placebo group.Neither the investigator nor the patient knew the group allocation. The placebo was identical to the intervention drug in appearance, labelling, and packaging, but did not contain any active ingredients.Supplies of tablets for every patient were identi? ed with

a three-digit number. A sealed envelope that contained the randomisation code for any given patient was kept by the

investigator and was not to be broken during the study,

except in cases of a serious life-threatening adverse event.

Opening of a certain envelope, whether intentional or

accidental, had to be carefully recorded on the related

case-report form, and the patient had to be withdrawn from the study. The steering committee and the independent party who did the statistics analysis were

blocked from all information about treatment allocations during the study.

After a 2-week run-in period, eligible patients with COPD were randomly assigned to receive carbocisteine (2×250 mg, three times daily) or placebo (two tablets, three times daily) for 1 year. Both carbocisteine and placebo tablets were provided by Baiyunshan Pharmaceutical, China. No other medications were provided as part of the study.After randomisation, patients were interviewed every

3 months until the end of trial to con? rm their vital signs, record any unscheduled visits to a health-care provider, check their adherence to the study regimen by collecting and counting the number of remaining tablets, record adverse events, and re? ll study tablets for the next 3 months.Conventional treatment for COPD, such as short-acting

or long-acting bronchodilators and inhaled corticosteroids,

Figure 1: Trial pro? le Correspondence to:

Nan-Shan Zhong, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of

Respiratory Disease, First A? liated Hospital of Guangzhou Medical College, Guangzhou 510120, China nanshan@https://www.doczj.com/doc/9718259282.html,

that had been started before the study, was permitted to continue but had to be sustained during the study period. Sys t emic administrations of corticosteroids, antibiotics, muco l ytics, or antitussive agents were not permitted unless con c omitant use of these agents were needed to treat exacerbation.

Outcome measures

The primary endpoint was exacerbation rate over 1 year. Exacerbation de? ned by Anthonisen17was used—ie, at least 2-day persistence of at least two major symptoms (worsening dyspnoea and an increase in sputum purulence, volume, or both), or of any single major symptom plus more than one minor symptom (upper airway infection, unexplained fever, and increased wheezing). Clinical data such as di? culty breathing, the amount and trait of sputum, fever, and presence of upper airway infection were followed-up using a patient diary card, and were reviewed between the patient and his or her attending physician at each interview before ? nal validation as an exacerbation by the steering committee. Secondary endpoints included covariance-adjusted exacerbation rate, quality of life, lung function and arterial oxygen saturation. Exacerbation rates strati? ed by months on treatment (3, 6, and 9 months) were also assessed. Quality of life was assessed by St George’s Respiratory Questionnaire (SGRQ) scores.18 The patients completed an SGRQ (using a validated Chinese version) before randomisation and at the end of study while they were clinically stable, under the supervision of clinical sta?trained on questionnaire administration.

At the start and end of the study, postbronchodilator spirometry was done according to American Thoracic Society recommendations for acceptability and repro-ducibility.19 FEV? was measured 20 min after inhalation of 400 μg salbutamol via a spacer. Predicted FEV? values were selected from the European Committee of Coal and Steel predictions20 and adjusted for Chinese ethnicity according to Zheng and Zhong’s recommen d ation21 to minimise variations from ethnic di? erences.

SpO? as measured by ? nger pulse oximetry was taken at the end of the run-in period and at 6 and 12 months of treatment. Adverse events were reviewed at each study interview.

Statistical analysis

Accurate calculation of sample size had been an issue of

great attention when planning the trial, but we were unable to do so because of a scarcity of reference data from previously published studies. Consequently, the sample size was determined on the basis of experiences of Chinese respiratory doctors and by the steering committee. The estimated sample size was deemed to be powered for this study.

All statistical analyses for baseline characteristics and outcomes were done on an intention-to-treat basis. Quanti-tative baseline characteristics and outcome measures were reported as means (SD) or as percentages within groups.

Exacerbation rate was analysed with a negative binomial

regression model including inter a ctions between treatment

and covariates (such as COPD stages, smoking status, and

concomitant medications). If interaction was not signi? -

cant, the treatment e? ect was assessed with a regression

model adjusted by covariant. Risk ratio and 95% CI in the

carbocisteine group versus placebo group were reported.

Log-rank test was used to compare the di? erence of

exacerbation in percentages between groups. SGRQ scores

Figure 2: Kaplan-Meier plot of probability of being exacerbation-free at each time point through the study

(total, symptom, activity, and impact score) and post-bronchodilator FEV

1

were analysed as changes from baseline values with Wilcoxon’s rank-sum test. χ2 test or Fisher’s exact test were used to compare the di? erence in percentages between groups.

Safety pro? les were assessed by safety set analysis. All hypothesis tests were two-sided, and p<0·05 was de? ned as signi?cant. No interim analysis was planned. All statistical analyses were done with a validated software package (SAS version 9.1).

Role of the funding source

The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had ? nal responsibility for the decision to submit for publication.

Results

Recruitment ran from June 1 to Sept 30, 2005, and the study was completed by Oct 15, 2006. 709 patients underwent randomisation (? gure 1). Of these, two patients (one in each group) were excluded because of ineligibility, but were included in the safety analysis. Non-signi? cant di? erence was found in the withdrawal rate between these two groups (13·60% vs 12·15%, χ2=0·332; p=0·565).

The two groups were similar in patient demographics, including history of smoking, duration and severity of COPD, baseline pulmonary function, quality of life, and base l ine medication (table 1). COPD stages II and III accounted for 88·1% (623 of 707) of the patients, with the rest being stage IV. Before this study, the most common bronchodilator used was xanthines, followed by β agonists and anticholinergics, whereas inhaled cortico s teroids were prescribed in only 16·7% (118 of 707) of patients.

Patient compliance was similar between the groups. The mean treatment duration was 341·2 days (SD 71·5) in the carbocisteine group and 342·6 days (SD 71·3) in the placebo group, with non-signi? cant di? erence between each other (Z=–0·599, p=0·549).

The 1-year cumulative number of exacerbations was 325 in the carbocisteine group and 439 in the placebo group, corresponding to 1·01 (SE 0·06) exacerbations per patient-year with carbocisteine treatment versus 1·35 (SE 0·06) with placebo (a 24·5% reduction). The risk ratio of exacerbation was 0·75 (95% CI 0·62–0·92, p=0·004). A Kaplan-Meier plot of the number of patients who were exacerbation-free at each time point through the study is shown in ? gure 2.

By analysing the covariance factors in our regression model, only two factors—COPD staging and concomitant therapy (theophylline and inhaled corticosteroids)—were found to signi? cantly a?ect COPD exacerbation. There were no signi?cant interactions between treatment and COPD stages (p=0·190 for treatment×COPD stage IV/ stage II; and p=0·159 for treatment×stage III/stage II). After adjusting for COPD stages, analysis of regression model excluding interaction showed favourable reduction

in the numbers of exacerbations in carbocisteine group compared with the placebo group (table 2). Similarly, no signi? cant interaction was noted between treatment and concomitant inhaled corticosteroids or inhaled corticosteroids naive. Fewer exacerbations were seen in the carbocisteine group than placebo group (risk ratio 0·75; 95% CI 0·63–0·91, p=0·004). The risk ratio adjusted by xanthines was 0·74 (95% CI 0·61–0·89, p=0·002). The advantage of carbocisteine over placebo in preventing an exacerbation was remarkable even after such adjustment. There were no signi?cant interactions between treatment and smoking status, and the risk ratio in exacerbation adjusted for smoking status was 0·74, 95% CI 0·64–0·86, p<0·0001.

Analysis of the length of treatment revealed that the prevention of exacerbation acted at month 6, when the risk ratio began to show statistical di? erences between the two groups (risk ratio 0·70 [95% CI 0·56–0·88], p=0·108 at 3 months; 0·79 [0·60–1·15], p=0·002 at 6 months; p=0·002 at 9 months 0·73 [0·60–0·89]).

Table 3 summarises the pretreatment and post-treatment quality of life in both groups. After a year of treatment, signi?cant changes from baseline in SGRQ total score (–4·06 units), symptom score (–11·34 units), and activity

score (–3·33 units) were detected in patients treated with carbocisteine but not placebo. The improvements in SGRQ total score and symptom score were regarded as clinically relevant. The SGRQ impact score did not show any change from baseline in either group. Postbronchodilator FEV? measurements were similar in each group before and after treatment, with no signi? cant di? erence between these two groups. as was di? erence in SpO? between the two treatments at each interview.

For the safety pro? les, 113 adverse events were reported during the study period (57 in the carbocisteine group and 56 in the placebo group). The most common adverse events reported (?ve events or more) were gastrointestinal and cardiac problems (14 cases and nine cases in the carbocisteine group vs?ve cases each in the placebo group). Table 4 summarises the adverse events. No deaths were reported in the study.

Discussion

The results of our study support previous ? ndings that long-term use of carbocisteine reduced the rate of exacerbations of COPD. The advantage of carbocisteine over placebo in prevention of an exacerbation was note-worthy, even after adjustment for COPD severity and concomitant therapy. We found no di? erence in exacerbation rate between the carbocisteine group and placebo group at early treatment (3 month), suggesting that longer use of carbocisteine was more e? ective for preventing exacerbations of COPD.

In addition to preventing COPD exacerbations, carbocisteine was shown to improve the patients’ quality of life. After 1 year of treatment with carbocisteine, signi? cant improvements over placebo were achieved in SGRQ (total and symptom scores). The activity score also seemed favourable with carbocisteine versus placebo.

The role of long-term mucolytic and antioxidation or anti-in? ammation therapy in COPD has attracted interest. Poole and Black15 did a systematic review in which 26 ran d omised, placebo-controlled studies recruiting 7335 par t icipants with COPD were included. Their data showed that treatment with mucolytics for at least 2 months sig n i?c antly reduced the number of exacerbations. The present study also showed preventive e?ects of carbo-cisteine on exacerbations when adjusted for concomitant use of inhaled corticosteroids. This ? nding di? ered from the BRONCUS study16 in which signi? cant reduction in exacerbation rate by N-acetylcysteine was shown only in patients without concomitant use of inhaled cortico-steroids. Several explanations might be reasonable for such di?erence. Firstly, inhaled corticosteroids were administered in only 16·7% of our study participants (table 1), compared with 70% of the BRONCUS16 partici-pants. Additionally, therapeutic inhaled cortico s teroids are generally prescribed in smaller doses to Chinese patients.22 As such, the e? ects of carbocisteine would be more readily identi? ed in our patients, with modest use of concomitant inhaled corticosteroids, than in the BRONCUS study. Secondly, carbocisteine showed a unique picture in terms of pharmacokinetics and drug actions (including probable inhibition of viral adherence to the airway11,23), and hence its di? erent e? cacy from N-acetylcysteine. Thirdly, the role of ethnicity in response to a treatment should be noted. The Chinese di?er from Europeans in dietary patterns, nutritional status, and lifestyle, which might speci? cally a?ect certain therapies. For instance, signi? cant di? erences in theophylline pharmaco k inetic constants were reported between American and Chinese children with asthma.24 Zhou and colleagues25 also showed that low-dose adminis-tration of theophylline signi?cantly reduced the time to ? rst exacer b ation and improved SGRQ scores in Chinese patients with COPD, which had not been reported in studies in white patients.

As the most important source of noxious, oxidant radical-rich gas, tobacco smoke represents a major risk factor for COPD. However, not all patients develop COPD because of smoking. In rural areas of developing countries like China, biomass fuel is also an important source of indoor air pollution.26 Unfortunately, non-smoking patients are excluded from many clinical studies related to COPD.27,28 Potential di?erences between smoking or non-smoking populations in the treatment of COPD were therefore not fully addressed. In a study by Zheng and co-workers,29 combination therapy with salmeterol and ? uticasone was seen to provide more bene? ts in COPD smokers than in non-smokers. We know of no study that has so far compared the e? ects of carbocisteine between smoking and non-smoking individuals. Our results showed signi?cantly fewer COPD exacerbations in carbocisteine-treated patients compared with placebo after adjustment for smoking status.

Prevention of acute exacerbations of COPD could lead to substantial savings in terms of healthcare use. Inhaled corticosteroids, long-acting β? agonists, and anti c holinergics would be preferable for better outcomes, yet mucolytics could be more a? ordable, and will continue to have a role in treatment of COPD, particularly for long-term use. For instance, the annualised cost per patient for carbocisteine therapy in China is 650 Yuan (US$90), but is about 4320 Yuan ($580) for combined treatment with inhaled

corticosteroids and long-acting β? agonists (more than six times higher). For many patients who cannot a? ord the combined t reatment f or c onventional t herapy, l ess-expensive mucolytics such as carbocisteine might be an important option, especially in low-income countries and regions. In our study, the direct cost of exacerbation was not analysed because of the incomplete data recorded from the study. Unlike in Europe and the USA, only a small percentage of people in China are covered by health insurance and reimbursement, and most have to pay for their medical services themselves. Since the uninsured group might not seek treatment because of ?nancial distress, we were unable to accurately calculate the medical costs.

There was no signi? cant improvement in lung function in the carbocisteine group compared with the placebo group after 1 year of treatment, which indicates that the reduced rates of of exacerbations and improvements in qual i ty of life were not due to bronchodilation e? ects. These ? nd i ngs were similar to those in other studies of mucolytics.15

Our study showed that the nature and incidence of adverse events were similar across the carbocisteine and placebo groups for 1 year, which were consistent with other studies using the same carbocisteine regimen. These results indicated that long term use of carbocisteine was well tolerated.

In conclusion, the 1-year management of carbocisteine was e? ective for COPD patients in terms of reductions in exacerbations and improvements in quality of life. There were no interactions between treatment and COPD severity, smoking status, and concomitant use of inhaled corticosteroids. Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for the long-term management of COPD.

Contributors

N-SZ and JK chaired the steering committee, designed the study protocol, organised the study, and ensured the intrinsic quality of the study. All other authors enrolled participants, collected data, and took responsibility for

their own centres. All authors contributed equally to this paper.

Con? ict of interest statement

Jin-ping Zheng won a Best Poster Travel Grant for COPD research from European Respiratory Society annual conference 2007 due to this work. We declare that we have no other con? ict of interest.

Acknowledgments

We would like to thank Kyorin Pharmaceutical, Japan, for ? nancial

support for the study; Mei Jiang (Guangzhou Institute of Respiratory Disease) and Beijing Contract Research Organisation (Beijing, China) for the statistical analysis; and Guang-qiao Zeng (Guangzhou Institute of Respiratory Disease) for his help with the manuscript.

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salmeterol (50 μg)/? uticasone propionate (500 μg) inhalation twice daily via accuhalar in Chinese patients with COPD. Chest 2007; 132: 1756–63.

DRGs与临床路径简介

一、DRGs简介

图 1 各国 DRGs 研究进展 图 1 中黄色的是已经开始运作 DRGs 的,已趋成熟;蓝色的是已经在做,处于成长过程中的;红色的是开始在做;绿色的是准备做的。从图中不难看出,进行 DRGs 研究的国家是很多的。 (三) DRGs 分组框架 DRGs 是由住院病例分为 25 个 MBC ( 主要诊断分类 ) ,再在 25 个 MBC 的基础上进行 DRGs 的分类。它的分组指标包括疾病的首要诊断、手术种类、并发症和合并症、出院状况(是否死亡)、年龄、昏迷时间和新生儿的体重,根据这些指标把 MBC 分为了若干个 DRGs 组,这些组在各个国家分组的数量不一样,它可以作为质量控制、费用补偿,易于管理。它依据资源消耗相近、临床特征相近进行分组。具体可见图 2 所示。 图 2 DRGs 分组框架 根据发病器官、系统和病因结构先划分成 25 个诊断分类组,详见表 1 。 表 1 25 个诊断分类组

图 3 DRGs 的形成 图 3 是在 25 个诊断相关分类以后分成的 DRGs ,它有手术室手术及操作和非手术室手术和操作,以及手术的分级、肿瘤症状,最后要按照年龄、伴随症和合并症进行分组。

DRGs的核心思想是将具有某一方面相同特征的病例归为一组,以方便管理。那么DRGs有哪些分组原则呢?

4. MCC (主要并发症 / 合并症) 对患者医疗资源消耗起到很大影响的并发症和合并症。 表 2 DRGs 分组情况 表 2 是 DRGs 的分组情况,美国 876 个,德国 986 个,法国 700 个,英国 583 个。 (六)应用效果 国外 20 余年的应用经验表明与现有的其他付费方式相比 DRGs 是一种相对合理的医疗费用管理方法和质量评价方法,既兼顾了政府、医院、患者等多方利益,又达到了医疗质量与费用的合理平衡。它可以兼顾各方利益达到质量与费用的合理平衡。 1. 效果一 能够控制医疗费用的增长。 DRGs 不再根据医院的投入,而是按照医院收治的病例及其诊断制定相应的补偿标准,使政府对医疗费用的控制更为直接有效。另一方面补偿标准的制定对医院起到了很好的约束作用,可以激励医院降低医疗成本从而节约卫生资源。 美国实施 DRGs 老年医疗保险住院总费用的增长速度从 1983 年的 18.5% ,降到 1990 年的 5.7%。手术费的增长率从 1984 年的 14.5% 降到 1992 年的 6.6% ,平均住院天数从 1980 年的 10.4 天降到 1990 年的 8.7 天, 1995 年已缩短到 6.7 天。 2. 效果二 提高医院的管理水平。 DRGs 定额预付制的实施给医院管理带来了一场深刻的变革,促进了医疗质量、经济、信息等方面管理学科的发展,涌现了临床路径、战略成本管理、数字化医院等先进管理手段,并且为医院进行同行间的评价和内部的管理提供了有效的手段。 3. 效果三 增加患者满意度。 DRGs 对医疗费用的控制,减轻了患者的就医负担,医院服务效率与服务质量的提

COPD患者的饮食指导

COPD患者的饮食指导 一.饮食指导的意义 慢性阻塞性肺病与高血压、糖尿病、以及恶性肿瘤等诸多慢性疾病一样,营养干预已成为疾病治疗环节中不可或缺的一部分。 1.改善能量负平衡 慢性阻塞性肺病患者因疾病所致的长期能量代谢失衡,普遍存在体质量下降及肌肉消耗。体质量下降,尤其是祛脂体质或称作瘦体群的下降,归根结底是能量的负平衡所致(韩锋锋,夏韶民,罗勇,2012)。瘦体群的下降直接影响患者的肌肉功能,包括呼吸肌的力量和运动耐力。而引起能量失衡的本质原因是热能摄入与消耗之间的不平衡(Schols AM, 2000)。过去的研究多集中于气道阻力增加引起的呼吸肌负荷和做功增加,而近期的一些报道认为由于慢性阻塞性肺病缓解期患者多存在骨骼肌形态的改变和代谢的异常,致使日常活动中无氧代谢的发生频率增加。而要限制活动量及降低静息能量消耗相对不易,故唯有通过营养干预,增加营养摄入来保证能量代谢平衡。 2.提高免疫功能, 营养失衡导致患者抗病能力的下降,免疫功能改变的结果易使患者的呼吸系统受到病原微生物的侵袭而发生肺炎,并使感染病程迁延,难以痊愈。免疫功能的下降影响了肺的防御机制。营养不良,呼吸道感染,呼吸衰竭等往往互为因果并形成恶性循环,有效的营养干预则有利于打破这种循环,改善患者的预后,降低住院率,提高生活质量(罗勇,徐卫国,杨玲,2003)。 3.平衡心理状态,利于康复 相比急性期患者,缓解期慢性阻塞性肺病患者精神紧张度高,焦虑、抑郁等负性情绪增多,厌食及恐惧进食的情绪障碍的发生率普遍高于一般人群。这与患者进食含碳水化合物较多的高热量食物期间所发生的缺氧和呼吸困难等表现有一定的关系,后者导致了患者就餐的恐惧心理(张鹏宇,陈文华,金先桥,2001)。因此,通过及时调整饮食结构和有效的营养干预有利于增进食欲,满足营养吸收和促进慢性阻塞性肺病的康复治疗。

肺功能检查指南

肺功能检查指南(第二部分)––肺量计检查 肺量计检查是肺功能检查中最常用的方法,采用肺量计测量呼吸容积和流量,两者可通过呼吸时间的微分或积分相互转换。肺量计分为两种:容积型肺量计通过密闭系统直接测量呼吸气体的容积,直观易懂,但仪器体积大,易于交叉感染,且呼吸阻力高,测定参数少;流量型肺量计则测量气体流量,呼吸阻力低,操作简单,体积小,清洁和维护方便,已逐渐取代容量型肺量计。

(一)肺量计技术标准 见。

1.测试环境的校准: 由于气体容积受环境温度、压力、湿度等因素的影响而变化,故肺量计检查时需将测试环境校准为生理条件,即正常体温(37 ℃)、标准大气压(760 mmHg,1 mmHg=kPa)及饱和水蒸气状态(BTPS)。若仪器已内置温度计和压力计,需确认其可靠性。2.肺量计校准: 是对实际测量值与理论值之间的误差进行校准。用于校准肺量计的校准仪,常称为定标筒,须精确到总量程的±%。校准时应确保肺量计与定标筒的连接无漏气、无阻塞。若校准超出范围应及时查找原因,必要时请专业人员检修。关键措施见。

容量计的质量控制:①每天检查是否漏气:封闭容量计的出口,给予≥ cmH2O(1 cmH2O=kPa)的持续正压,若1 min后容积减少>30 ml则存在漏气。②每天用定标筒检查容积精确度,误差应≤±3%。③每个季度检查容积线性,方法有2种,一种以1 L 容积递增,连续注入肺量计,如0~1、1~2、2~3、……、7~8 L;另一种初始容积以1 L递增,以3 L容积分次注入肺量计,如0~3、1~4、2~5、3~6、4~7和5~8 L。比较相应的累积容积与实测容积的差异,若误差均符合容积精确性要求,则其容积线性可接受。 流量计的质量控制:①校准:每次启动流量计均需经定标筒校准,误差应≤±3%,校准后可获得一个校准系数。流量计检查的结果是以传感器计量的数值乘以校准系数所得的。②校准验证:每天都应用定标筒在~L/s范围内以不同流量进行校准验证,至少操作3次,误差应≤±3%。③线性验证:每周还需以低、中、高3种不同的流量~、~和~L/s)进行流量线性验证,每种流量至少操作3次,每种流量对应的容积误差均应≤±3%。 标准呼吸模拟器校准:某些肺功能实验室和厂家还会采用微机控制的气泵,称为标准呼吸模拟器,产生多种标准波形(如ATS 的24个FVC波形和26个PEF波形)的气流,气流通过肺量计,对比肺量计的测量值与模拟器的标准值之间的差异,即为肺量计的误差。我国的肺功能仪校准规范推荐定期用标准呼吸模拟器对肺功能仪进行质量检测,并可获得权威机构签发的证书。 1.检查前应详细询问受试者的病史,判断肺量计检查的适应证,排除禁忌证,并了解受试者的用药情况。 2.准确测量身高和体重:详见肺功能指南第一部分。 3.体位:取坐位,测试时应挺胸坐直不靠椅背,双脚着地不翘腿,头保持自然水平或稍微上仰,勿低头弯腰俯身。正确的坐姿有助于受试者获得最大的呼吸量。若采用站位或卧位,应在报告中说明。 4.检查动作的练习:检查前应先向受试者介绍及演示检查动作,并指导受试者进行练习。也可播放演示录像,有助于受试者更快地掌握动作要领。 肺量计检查主要包括慢肺活量、用力肺活量及最大自主通气量3部分内容,其中慢肺活量检查将在肺容量检查部分详细介绍,本章主要介绍用力肺活量和最大自主通气量检查。 (一)FVC FVC是指最大吸气至肺总量(TLC)位后,做最大努力、最快速度的呼气,直至残气量(RV)位所呼出的气量。用力呼气时单位时间内所呼出的气量又称为时间肺活量。 1.检查程序分为4个阶段()。 图1 FVC检查的程序 2.测试曲线和指标:容积-时间曲线(V-T曲线)是呼气时间与容积变化的关系曲线()。流量-容积曲线(F-V曲线)是呼吸气体流量随肺容积变化的关系曲线()。曲线形状和指标大小取决于呼气力量、胸肺弹性、肺容积及气道阻力对呼气流量的综合影响。在F-V曲线的起始部分,呼气肌的长度最长,收缩力最大,流量也最大,图形上表现为流量迅速增至峰值,其值与受试者的努力程度有关,故称为用力依赖部分。在曲线的终末部分,呼吸肌长度显着缩短,收缩力显着降低,呼气流量与用力无关,流量的大小与小气道的通畅程度密切相关,故称为非用力依赖部分。T-V曲线和F-V曲线上的常用指标:(1)FVC:指完全吸气至TLC 位后以最大的努力、最快的速度做呼气,直至残气量位的全部肺容积。在正常情况下,VC与FVC相等。但在气流阻塞的情况下,用力呼气可致气道陷闭,VC可略大于FVC。(2)t秒用力呼气容积(FEVt):指完全吸气至TLC位后在t秒以内的快速用力呼气量。按呼气时间,可分为、、FEV1、FEV3和FEV6等指标,分别表示完全吸气后在、、1、3、6 s的用力呼气量。(3)一秒率(FEV1/FVC ):是FEV1与FVC的比值,常用百分数(%)表示,是判断气流阻塞的主要指标。气流阻塞时,给予充足的呼气时间,受试者可充分呼

肺功能检查

肺功能检查 肺功能检查肺功能检查是呼吸系统疾病的必要检查之一,对于早期检出肺、气道病变,评估疾病的病情严重程度及预后,评定药物或其它治疗方法的疗效,鉴别呼吸困难的原因,诊断病变部位、评估肺功能对手术的耐受力或劳动强度耐受力及对危重病人的监护等方面有重要的指导意义。项目肺功能检查包括通气功能、换气功能、呼吸调节功能及肺循环功能等,检查项目及测定指标众多.过去的肺功能仪主要以机械和化学方法检测为主,测定烦琐,费时费力,而且检测误差较大,限制了其在临床上的广泛应用,医务工作者对其知识也了解有限。近年来,随着科学技术的发展,新的检测技术的出现,尤其是电子计算机的应用,使肺功能检测技术得到了很大的发展,其在临床上的重要性也愈益受到重视。目的肺功能检查主要用于以下目的:1、早期检出肺、呼吸道病变。2、鉴别呼吸困难的原因,判断气道阻塞的部位。3、评估肺部疾病的病情严重程度。 4、评估外科手术耐受力及术后发生并发症的可能性。 5、健康体检、劳动强度和耐受力的评估; 6、危重病人的监护等。特点1、肺功能检查是一种物理检查方法,对身体无任何损伤,无痛苦和不适。2、肺功能检查具有敏感度高、重复检测方便和病人易于接受等优点。3、

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COPD的营养支持

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