Objective To evaluate and select essential antihypertensive medicine using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five clinical guidelines on hypertension were included, two of which were evidence-based. (2) Totally there were nine classes and 70 antihypertensive medicines listed in the guidelines. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines, and the quantity and quality of evidence, we offered a b recommendation for nifedipine, verapamil and enalapril and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. We made a recommendation against furosemide and timolol due to the lack of evidence from guidelines. (4) Nine recommended medicines have been marketed with the dosage forms and specifications corresponding to guidelines in China. The prices of metoprolol, amlodipine and enalapril were higher than those of other six (daily cost: metoprolol 3.80 to 7.60 yuan, amlodipine 2.16 to 4.32 yuan, and enalapril 0.86 to 6.88 yuan). As a whole, the prices of recommended antihypertensive medicine were affordable. (5) Results of domestic studies indicated that three bly-recommended medicines (including nifedipine, verapamil and enalapril) were safe, effective, economical and applicable. Conclusion (1) We offer a b recommendation for nifedipine, verapamil and enalapril as antihypertensive medicine and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. (2) There is lack of high-quality evidence from relevant domestic studies, especially on long-term safety and pharmacoeconomic evidence. (3) We propose that more studies should be carried out on the safety, efficacy and pharmacoeconomics of six medicines for which we make a weak recommendation to produce high-quality local evidence.
Objective To evaluate and select essential medicine for diabetes mellitus based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Six guidelines were included, three of which were evidence-based and published from 2006 to 2011. (2) Five recommended medicines were included according to recommendations and evidence of WHOEML (2011), NEML (2009), CNF (2010) and other guidelines. They were metformin, glibenclamide, glipizide, rosiglitazone and pioglitazone. Domestic evidence of the first three drugs was evaluated. (3) The first three have been marketed with the specifications and dosage forms corresponding to guidelines in China. The FBG cost-effectiveness ratios of metformin with different dosage forms as immediate release compressed tablet, enteric-coated tablet and sustained release capsule were 3.37, 3.76 and 3.50 respectively. 2-hour BG cost-effectiveness ratios of metformin were 3.74, 4.00 and 3.71 respectively. The cost-effectiveness ratio of glibenclamide and glimepiride were 11.23 and 13.81 respectively. Conclusion We offer a recommendation for: (1) Metformin (immediate release tablet/capsule for oral use, 0.25 g), contraindicated in patients with renal insufficiency. (2) Glibenclamide (tablet, 2.5 mg; capsule, 1.75 mg) and glipizide (tablet, 2.5 or 5mg; dispersible tablet, 5 mg), contraindicated in children, women during pregnancy or lactation, patients in the perioperative period of major operation, patients after total pancreatectomy, and patients allergic or adversely reacted to sulfa drug. (3) Evidence-based and standardized primary healthcare guidelines as well as clinical and pharmacoeconomic studies on diabetes mellitus (large-scale, multi-centre, randomized and double-blinded) are needed to produce high-quality local evidence.
Objective To evaluate and select essential medicine for acute bronchitis using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Eight guidelines were included (seven foreign guidelines, one domestic guideline; five based on evidence, three based on expert consensus). (2) A result of six RCTs (n=816, low quality) indicated that pentoxyverine had efficiencies of 53% to 82% for cough relief. Among the six RCTs, a result of three RCTs (n=283) indicated that pentoxyverine was slightly less efficient than procaterol (RR=0.86, 95%CI 0.78 to 0.94, P=0.001); a result of two RCTs (n=233) indicated that pentoxyverine was slightly less efficient than Chinese medicinals decoction (RR=0.82, 95%CI 0.74 to 0.91, Plt;0.001). Adverse reaction of pentoxyverine (incidence: 0% to 2.4%) mainly covered nausea, palpitation, etc. Pentoxyverine cost 0.20 yuan (for adult) or 0.08 yuan (for child) daily, which was orally taken and applicable to the target population. (3) A result of six RCTs (n=403, low quality) indicated that the efficiencies of dextromethorphan for cough relief was 47.0% to 95.3%. Among the six RCTs, a result of one RCT (n=283) indicated that dextromethorphan hydrobromide (nasal drop) was more efficient than blank intervention (RR=3.71, 95%CI 1.91 to 7.21); a result of one RCT (n=43) indicated that dextromethorphan (for oral use) was more efficient than placebo (RR=1.74, 95%CI 1.13 to 2.66); a result of one RCT (n=300, moderate quality) indicated that dextromethorphan was more efficient than pentoxyverine (RR=1.16, 95%CI 1.07 to 1.26); a result of one observational study (n=121, low quality) indicated that dextromethorphan given for 5 days had an efficiency of 66.5%. Adverse reaction of dextromethorphan (incidence: 2% to 30%) mainly covered mouth dryness, dizziness, nausea, etc. Conclusion (1) We offer a b recommendation for dextromethorphan used in relieving dry cough due to acute bronchitis. (2) We offer a weak recommendation for pentoxyverine as symptomatic treatment for cough relief. (3) We make a recommendation against antibiotics, β2-agonist bronchodilators and mucolytic agents as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies of acute bronchitis in hopes of producing high-quality local evidence.
Objective To evaluate and select essential medicine for community-acquired pneumonia (CAP) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Eleven guidelines were included (nine foreign guidelines, two domestic guidelines; nine based on evidence, two based on expert consensus). For CAP, amoxicillin amp; clavulanate potassium had efficiencies of 77.1% and an incidence of 18.8% as to adverse reaction that mainly included gastrointestinal reaction, skin rashes, etc. Piperacillin/tazobactam had an efficiency of 92.1% and a bacterial clearance rate of 88.9%. Cefuroxime had an efficiency of 89% and a bacterial clearance rate of 85.5%. There was no statistical significance between azithromycin and cefuroxime for CAP (RR=0.98, 95%CI 0.9 to 1.06); however, azithromycin was superior to cefuroxime in shortening fever-relief time (MD=–0.98, 95%CI –1.24 to –0.55) and cough-relief time (MD=–1.36, 95%CI –1.94 to –0.78). Efficiencies of ceftriaxone, cefotaxime, moxifloxacin and lavofloxacin were all more than 80% and among the three, moxifloxacin was the most efficient (RR=1.08, 95%CI 1.02 to 1.13, P=0.004). Meropenem had an efficiency of 90%, a bacterial clearance rate of 83.3% and an incidence of 3.33% as to adverse reaction that mainly included diarrhea. Conclusion (1) We offer a b recommendation for antibiotics such as amoxicillin, amoxicillin amp; clavulanate potassium, ampicillin/sulbactam, piperacillin/tazobactam, doxycycline, azithromycin, clarithromycin, cefuroxim, ceftriaxone, cefotaxime, lavofloxacin, moxifloxacin, ertapenem, meropenem, imipenem and vancocin. (2) We offer a weak recommendation for penicillin G, ciprofloxacin and erythromycin. (3) We propose that doctor should choose optimal antibiotics based on commonly-seen pathogenic bacteria that cause CAP, local criteria of antibiotic susceptibility, severity of CAP, and risk factors of patients.
Objective To evaluate and select essential medicine for bone fracture using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) 17 guidelines were included, six of which were evidence-based or based on expert consensus. We found that for fracture, global guidelines recommended surgical treatment and analgesics, while domestic guidelines recommended Chinese patent drugs. (2) A result of one RCT (low quality) indicated that Shang Ke Jie Gu Pian (name of a Chinese patent drug) shortened the clinical recovery time of fracture (MD=–4.2, 95%CI –5.25 to –3.14). A result of one RCT indicated that Shang Ke Jiu Ji Pian had a higher total clinical efficiency compared with San Qi Pian (name of a Chinese patent drug) (RR=1.28, 95%CI 1.11 to 1.47). A result of one RCT (low quality) indicated that Shang Ke Jiu Ji Pian (name of a Chinese patent drug) had a better effect than Shenyang Hong Yao Pian (name of a Chinese patent drug) in promoting the growth of osteotylus (RR=1.48, 95%CI 1.27 to 1.73) and also it had a higher clinical recovery rate (RR=1.62, 95%CI 1.37 to 1.9) compared to Shenyang Hong Yao Pian. A result of one RCT (moderate quality) indicated that Shang Ke Jiu Ji Pian was slightly better than Die Da Wan (name of Chinese patent drug) in regard to the recovery score of fracture (MD=0.25, 95%CI 0.026 to 0.47). A result of one RCT (low quality) indicated that compared to fracture reduction alone Shang Ke Jiu Ji Pian efficiently relieved pain (MD=–25.9, 95% –32.6 to –19.19) and shortened pain time (MD=–38.6, 95% –41.44 to –35.77). A result of one quasi-RCT (low quality) indicated that Shang Ke Jiu Ji Pian had a higher efficiency in relieving pain than benorylate (RR=1.13, 95%CI 1.04 to 1.23). A result of one RCT (low quality) indicated that Shang Ke Jiu Ji Pian had a higher efficiency than Shenyang Hong Yao Pian in relieving pain and swelling (RR=2.4, 95%CI 1.88 to 3.02). A result of one RCT (moderate quality) indicated that Shang Ke Jiu Ji Pian was superior to Die Da Wan in relieving pain and swelling (MD=–0.4, 95%CI –0.60 to –0.2). A result of two RCT (n=198) indicated that Shang Ke Jie Gu Pian caused no adverse reaction. With good applicability, Shang Ke Jie Gu Pian (taken with warm water or rice wine) cost 7.47 yuan daily. Conclusion (1) We offer a b recommendation for Shang Ke Jie Gu Pian and Jie Gu Qi Li Pian used in the treatment of adult fracture. (2) We should carry out more large-sample and controlled trials and improve outcome indicator in order to produce high-quality local evidence.
Objective To systematically evaluate the influencing factors, intervention measures and management mode of epilepsy patients in China, so as to provide evidence support for ensuring the therapeutic effect of epilepsy patients. Methods PubMed, EMBASE, Cochrane Library, CBM, CNKI, VIP, Wanfang and other domestic and foreign databases were systematically searched, and the literature on influencing factors, intervention measures and management modes of self-management behavior of epilepsy patients in China was included. Descriptive methods were used to analyze the results. Results A total of 21 studies were included, including 2 studies on influencing factors, 14 studies on intervention measures and 5 studies on management mode. The participants of 20 studies is adult epilepsy patients, and one study is adolescent epilepsy aged 13 ~ 17, with a sample size of 40 ~ 327 cases and a median sample size of 70 cases. The results showed that self-management behavior is positively correlated with self-efficacy, bachelor degree or above, female and operation duration < 3 hours, and negatively correlated with 30 ~ 50 years old. The self-management behavior scale score, medication compliance, treatment satisfaction, quality of life, seizure frequency, symptom checklist, anxiety and depression score in the intervention group were better than those in the control group. After the intervention of self- management mode, the self-management score, treatment efficiency, quality of life and medication compliance of the intervention group were better than those of the control group. Conclusions The level of self-management of epilepsy patients in China is insufficient, and the influencing factors and intervention measures are single, lacking integrated intervention measures and management models based on different levels of individuals, families, medical system and society. It is suggested that the self-management model of epileptic patients should be constructed based on evidence to improve self-efficacy and self-management level.
Objective To evaluate and select essential medicine for uterine neoplasms using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Six guidelines were included, three of which were evidence-based. (2) Retrieved guidelines related to nine medicines (of three classes) for uterine neoplasms and five adjuvant drugs (of three classes) used after relevant surgery. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guideline and the quantity and quality of evidence, we offered a b recommendation for medroxyprogesterone acetate, oxytocin, ergometrine and a weak recommendation for testosterone propionate, methyltestosterone, tamoxifen, mifepristone, tranexamic acid, leonurus heterophyllus used in the treatment of uterine neoplasms. We offered a recommendation against danazol and aromatase inhibitors. (4) We found relevant domestic literature on mifepristone, methyltestosterone, tamoxifen, oxytocin and leonurus heterophyllus. Mifepriston combined with methyltestosterone or tamoxifen was recommended to use as a conservative therapy for uterine neoplasms. Oxytocin,and leonurus heterophyllus were used to reduce bleeding after the surgery of uterine neoplasms. As to daily expense, mifepriston (25 mg/d) cost 13.0 to 27.5 yuan, methyltestosterone (5 mg/d) 0.074 yuan, tamoxifen (20 mg/d) 0.6 to 1.4 yuan, leonurus heterophyllus (injection, 1 mL) 15 yuan and oxytocin (injection, 20 U) 1.5 yuan. (5) Results of domestic studies indicated that mifepristone, mifepristone plus methyltestosterone, and mifepristone plus tamoxifen were proved to be safe and applicable for the treatment of uterine neoplasms. Oxytocin and leonurus heterophyllus are effective in preventing postoperative bleeding and the combination of two effectively and safely promoted uterine contraction. Conclusion (1) We offer a recommendation for three medication plans used in the treatment uterine neoplasms during perimenopause, including: a) Mifepristone (25 mg/ tablet, once daily); b) Mifepristone (25 mg/ tablet, once daily) plus methyltestosterone (5 mg/tablet, once daily); c) Mifepristone (25 mg/ tablet, once daily) plus tamoxifen (10 mg/tablet, twice daily). The three plans mentioned above should be used from first day of menstrual cycle, continuously for three months. (2) Adjuvant drugs such as oxytocin (injection, 1 to 2 mL) and leonurus heterophyllus (injection, 10 U) can be applied to reduce vaginal bleeding flow after the surgery of uterine neoplasms. (3) Personnel in elementary healthcare institution should stick to drug indication, carefully make follow-up, and dynamically monitor the change of uterine neoplasms and menstruation so as to adjust medication plan according to patients’ situation.
Objective To establish standards, methods and processes for evidence-based evaluation and selection of essential medicine that meet the needs of the 8 pilot township health centers in China. Methods A descriptive analysis was conducted to compare the similarities/differences and the advantages/disadvantages of the standards, methods and processes between the World Health Organization (WHO) essential medicines evaluation and selection, and the GRADE evidence quality and recommend intensity. In combination with the former outcomes of this series of study, the standards, methods and processes of evidence-based evaluation and selection of essential medicines in the domestic pilot township health centers were optimized, restructured and improved. Softwares such as GRADEprofiler were used to assess the quality of evidence. Results a) Localized standards, methods and processes for evidence-based evaluation and selection of essential medicine were established, and the evaluation tool was ascertained; and b) Disease and drug names, guidelines and searching processes for evaluation and selection of essential medicine were developed with standardized, systematic and transparent approaches. Conclusion a) Standards, methods and processes for searching, evaluating and recommending the best evidence are preliminarily established, through comparative analysis on the effectiveness, safety, cost-effectiveness and applicability of the candidate medicines for diagnosing, treating and preventing diseases in township health centers in China; b) Following the principle of “utilizing the best existing evidences and developing the urgently-needed but lacking evidence”, a good exploration was done for the localization, standardization and transparency of the standards, methods and processes of evidence-based evaluation and selection of essential medicine for pilot township health centers.
Objective To evaluate and select essential medicine for acute gastroenteritis using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines were included, two of which were evidence-based. (2) Recommended medicines included eight antidiarrheals (of four classes) and three antemetics. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines and the quantity and quality of evidence, we offered a weak recommendation for ondansetron, metoclopramide, smectite, racecadotril and loperamide applied in the treatment of acute gastroenteritis. We made a recommendation against antibiotics, dexamethasone, kaolin-pectin, activated charcoal, attapulgite and bismuth subsalicylate. (4) Evidence from domestic studies: a result of 14 CCTs (n=1 635, low quality) indicated that in the significant efficiency and total efficiency, smectite (smecta) was superior to routine liquid infusion, norfloxacin, gentamicin or furaxone. Among these 14 CCTs, two CCTs reported smectite (smecta) caused nausea and vomiting (three cases); one CCT reported pain and distention in the abdomen (one case) and general discomfort (one case); and the rest reported no adverse reaction. A result of 10 CCTs (n=1 017, low quality) indicated that for acute diarrhea, racecadotril was superior to routine treatment in the significant efficiency (OR=2.55, 95%CI 1.64 to 3.94, Plt;0.01) and total efficiency (OR=4.32, 95%CI 2.96 to 6.30, Plt;0.01). A result of two CCTs (n=344, low quality) indicated that racecadotril was superior to smectite in the total efficiency in treating acute diarrhea. A result of two CCTs (n=1 056, low quality) indicated that racecadotril was superior to routine treatment in the total efficiency in treating acute adult diarrhea (OR=5.19, 95%CI 3.54 to 7.63, Plt;0.01). A result of two CCTs (n=182, low quality) reported children presented with nausea (two cases). A result of one CCT (n=947, low quality) reported adults presented with constipation (fifteen cases), anorexia (four cases), headache (nine cases) and abdominal pain (one case). Conclusion For acute gastroentitis, we offer a weak recommendation for smectite (powder, for oral use) used in adults (once 3 g, tid., mixed with warm water before intake), child under one year of age (3 g daily, bid.), and child above one year of age (once 3 g, qd. or bid.). Retention enema could be appiled to children with acute gastroenteritis. We also offer a weak recommendation for racecadotril (capsule) used in adults (one capsule, tid., taken continuously less than seven days). Due to the lack of evidence from clinical trials, we make a recommendation against racecadotril applied to women with pregnancy and lactation or children. In order to produce high-quality local evidence, we propose that (1) Further clinical studies should be standardized in diagnosis and criteria. (2) The design and implementation quality of clinical studies should be improved. (3) Original studies on pharmacoeconomic studies and drug applicability are needed.