中国老年门诊患者潜在不适当用药现状系统评价

目的:了解中国老年门诊患者潜在不适当用药的现状及相关影响因素。方法:系统搜索中国生物医学文献服务系统(Sino Med)、中国知网(CNKI)、万方数据库、Pub Med、Embase和Web of Science的相关文献(截至2017年9月),纳入研究为横断面研究,研究对象是中国老年门诊患者,并且使用了潜在不适当用药的筛查工具,数据分析采用STATA软件。结果:共纳入文献16篇,其中有11篇研究使用了Beers标准(2012版),5篇使用了中国PIM目录;根据Beers标准,PIM的总体发生率为14.8%(95%CI:13.2%~16.4%)。根据中国PIM目录,PIM的总体发生率为23.2%(95%CI:19.3%~27.1%)。相关影响因素包括性别、年龄、用药种类和合并疾病种类。常见的不适当用药的药物种类:苯二氮类药物、甲氧氯普胺、螺内酯、非甾体抗炎药、胺碘酮和氯吡格雷。结论:虽然中国老年门诊患者PIM的发生率相对较低,但是应该引起医疗机构的重视;合理使用潜在不适当用药筛查工具,促进老年门诊患者合理用药。     

中国老年住院患者潜在不适当用药现状研究

目的探讨中国老年住院患者潜在不适当用药(PIM)的发生率以及相关影响因素。方法系统检索中国生物医学文献服务系统、中国知网、万方数据库、维普网、PubMed和Web of Science的相关文献(截止至2017年3月)。纳入文献类型为回顾性,对象是中国老年住院患者,并且使用了潜在不适当用药的筛查工具。排除只关注一种不合理问题或只针对某种疾病老年患者的研究。数据分析采用STATA软件。结果共纳入文献26篇,潜在不适当用药的总体发生率为33.9%(95%CI:24.5%~43.2%;范围:13.3%~82.8%)。其中有20篇研究使用了Beers标准,2篇使用了STOPP/START标准,4篇联合使用了Beers标准和STOPP/START标准。相关因素包括性别、年龄、用药种类、合并疾病种类、住院天数、付费方式等;常见的不适当用药的药物种类:苯二氮艹卓类药物、心血管系统药物、抗胆碱药物、非甾体抗炎药和甲氧氯普胺。遗漏率较高的药物为抗血小板药物、他汀类药物及二甲双胍。结论中国老年住院患者潜在不适当用药的发生率仍然很高。高龄、多重用药、合并症数量及住院天数是影响老年住院患者潜在不适当用药发生的重要影响因素。     

Medical management of endometriosis: a systematic review

Endometriosis is an important clinical problem in routine practice. Besides the problems of dysmenorrhea, dyspareunia and chronic abdominal pain, women with endometriosis are often infertile. We performed a systematic literature review on two issues: firstly, we clarified which medical treatment options have been investigated in prospective, randomized studies. Secondly, potential future treatments, still being preclinically investigated, were examined. A meta-analysis was not possible as the studies varied too much in their protocols and inclusion and exclusion criteria, as well as in the drugs and doses administered. Gonadotropin-releasing hormone (GnRH) agonists, progestins and oral contraceptives all appear to offer certain advantages for endometriosis patients. GnRH agonists appear to be the most effective but they are expensive and long-term treatment is not possible because of loss of bone mineral density. Estrogen add-back may offer some benefit for the clinical complaints of patients, but it may reduce the efficacy of GnRH agonists. Progestins have the best clinical profile and a good cost-effectiveness balance; however, most studies found that they were not as effective as GnRH agonists. Oral contraceptives are only effective during treatment and have a high relapse rate after therapy is completed. Future options may include the use of GnRH agonists, selective estrogen receptor modulators (SERMs) and anti-estrogens, as well as immunomodulators.     

拉莫三嗪治疗儿童及青少年失神性癫痫的系统评价

目的 系统评价拉莫三嗪治疗儿童及青少年失神性癫痫的疗效和安全性。方法 通过PubMed、The Cochrane Library、EMbase、维普、万方、CBM和CNKI数据库进行检索,检索时限均为从建库至2014年8月,收集拉莫三嗪治疗儿童及青少年失神性癫痫的临床试验资料。由两位研究者按照纳入与排除标准,独立进行文献筛选、资料提取,评价纳入研究的方法学质量,采用RevMan 5.2软件进行荟萃分析。结果 共纳入7项研究,721例患儿。纳入研究文献质量评价结果是,A级2篇,B级3篇,C级2篇。荟萃分析结果显示:拉莫三嗪单药治疗儿童及青少年失神癫痫疗效优于安慰剂,但弱于丙戊酸和乙琥胺。拉莫三嗪常见不良反应发生率与丙戊酸、乙琥胺无显著性差异。结论 拉莫三嗪单药治疗儿童及青少年失神性癫痫的疗效确切,耐受良好。对于使用丙戊酸或乙琥胺不耐受的患者来说,拉莫三嗪是一种较好的选择。     

Determinants of inappropriate empirical antibiotic treatment: systematic review and meta-analysis

This systematic review assessed study-level determinants of non-covering (inappropriate) empirical antibiotic treatment (IEAT), focusing on the influence of study years and the prevalence of multidrug-resistant organisms (MDROs) in the study. Prospective and retrospective observational studies reporting on the association between IEAT and mortality in adult patients with microbiologically documented infections published between 2008–2016 were included. A meta-analysis of IEAT rates was conducted using a random-effects model. Subgroup analyses and mixed-effect single-covariate meta-regression were conducted to identify the association between clinical and methodological study-level covariates and IEAT rates. Heterogeneity was assessed using the I² measure of inconsistency. Multi-covariate meta-regression was conducted including variables with a P-value of <0.1 on single-covariate analysis. A total of 191 studies were included assessing 73 595 patients, most commonly with bacteraemia. The pooled IEAT event rate was 32% [95% confidence interval (CI) 30–35%], with large heterogeneity (I²?=?97.7%). On multi-covariate analyses, the prevalence of any MDRO [odds ratio (OR) per 10% increase in prevalence?=?1.11, 95% CI 1.07–1.15], Acinetobacter spp. specifically (OR?=?1.99, 95% CI 1.22–3.25) and advancing study years were associated with IEAT rates (OR?=?1.03, 95% CI 1.00–1.06 per year). MDRO rates were independently associated with mortality rates in the studies, adjusting to the rate of IEAT. The prevalence of MDROs, mainly multidrug-resistant Gram-negative bacteria, is significantly associated with the probability of prescribing IEAT and mortality rates in recent studies. We show how antibiotic resistance impacts patient management and outcomes.     

Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review

Objective: We conducted a systematic review to assess the efficacy and safety of Thrombopoietin-receptor agonists (TPOras) for pediatric immune thrombocytopenia (ITP).

Methods: We searched PubMed, Embase and Cochrane Library from their earliest records to January 2017. Randomized controlled trials (RCTs) were included. Primary outcomes were durable response and clinically significant bleeding. Secondary outcomes were overall response, overall bleeding events, the use of rescue medication and adverse events (AEs).

Results: Five randomized RCTs (261participants) were included. Compared with placebo group, the proportion of patients achieving durable platelet response was significantly higher in Eltrombopag (P = 0.0004) or Romiplostim (P = 0.002) group, so was the overall response in Eltrombopag [RR = 2.64, 95% CI (1.58, 4.44)] or Romiplostim [RR = 5.05, 95% CI (2.21, 11.53)] group. Both clinically significant bleeding (P = 0.04) and total bleeding (P = 0.01) in Eltrombopag group were significantly less frequent than those in placebo group, while no significant difference between Romiplostim and placebo group. The proportion of patients receiving rescue medication, the incidence of overall AEs and serious AEs between TPO-receptor agonists and placebo group were not significantly different.

Conclusion: TPOras might improve both durable and overall platelet response in pediatric ITP, compared with placebo.     

Antipsychotic poisoning in young children: a systematic review.

The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment.In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children potentially ingesting a toxic dose or who are symptomatic should be considered for assessment in hospital. Most cases resolve with good supportive care. Toxic doses are only estimates that are based on limited data and should be used with caution until prospective studies are undertaken.     

Pharmacological agents for developmental stuttering in children and adolescents: a systematic review

Stuttering affects approximately 5% of children up to the teenage years. There are many possible forms of intervention, one of which is pharmacotherapy. No review about the treatment of stuttering with pharmacological agents in children and adolescents has been undertaken. The objectives of this review were to determine the extent of previous research in this area and to assess the success of pharmacological agents in reducing the frequency of disfluency in child and adolescent stutterers (<18 years). A systematic search of MEDLINE, PsychInfo, Embase, and Cochrane Systematic Review databases was carried out to identify potential studies for the review. Studies that met specified criteria were selected for detailed examination, and the quality of evidence they provided was assessed according to 7 criteria that pertained to study design and data provision. Seven publications met the inclusion criteria for the review. Only 1 publication was classified as strong evidence quality, and this reported that clonidine did not reduce the frequency of disfluency in a group of 25 individuals who stuttered. All further publications were classified as either very low or low evidence quality. The agents examined were risperidone, olanzapine, clonidine, tiapride, haloperidol, and chlorpromazine.     

Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review

ABSTRACT

Introduction: Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children’s lives and their families.

Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4–18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles.

Expert commentary: Three RCTs (256 children with FD, 2–16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6–75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed.

Abbreviations: AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; H₂RAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants     

Thiopurine monitoring in children with inflammatory bowel disease: a systematic review

Aims

The aim was to systematically review the evidence on the clinical usefulness of thiopurine metabolite and white blood count (WBC) monitoring in the assessment of clinical outcomes in children with inflammatory bowel disease (IBD).

Methods

Medline, Embase, Cochrane Central Register of controlled trials and http://www.clinicaltrials.gov were screened in adherence to the PRISMA statement by two independent reviewers for identification of eligible studies. Eligible studies were randomized controlled trials (RCTs), cohort studies and large case series of children with inflammatory bowel disease (IBD) (<18 years) who underwent monitoring of thiopurine metabolites and/or WBC.

Results

Fifteen papers were identified (n = 1026). None of the eligible studies were RCTs. High 6-thioguanine nucleotide (6TGN) concentrations were not consistently associated with leucopenia. Leucopenia was not associated with achievement of clinical remission. A positive but not consistent correlation between 6TGN and clinical remission was reported. Haematological toxicity could not be reliably assessed with 6TGN measurements only. A number of studies supported the use of high 6-methylmercaptopurine ribonucleotides (6MMPR) as an indicator of hepatotoxicity. Low thiopurine metabolite concentration may be indicative of non-compliance.

Conclusion

Thiopurine metabolite testing does not safely predict clinical outcome, but may facilitate toxicity surveillance and treatment optimization in poor responders. Current evidence favours the combination of thiopurine metabolite/WBC monitoring and clinic follow-up for prompt identification of haematologic/hepatic toxicity safe dose adjustment, and treatment modification in cases of suboptimal clinical outcome or non-compliance. Well designed RCTs for the identification of robust surrogate markers of thiopurine efficacy and toxicity are required.     

Erythropoietic growth factors for children with cancer: a systematic review of the literature

ABSTRACT

Objective: To review evidence on the use of erythropoietic stimulating agents (erythropoietin or darbepoetin) in children with cancer.

Methods: A systematic review of the published literature was performed using MEDLINE (1966–July 2007) and references from a Cochrane systematic review (focusing mainly on adults) published in 2006.

Results: The review identified 12 studies, comprising five randomized trials, six case control studies and one open-label, dose-escalation study. All the studies that used adequate doses of recombinant human erythro­poietin (rhEPO) (usually 150?IU/kg three times per week) demonstrated benefits for rhEPO except for one study in which rhEPO was added to G-CSF in children with high-risk neuroblastoma. Despite the heterogeneity of the populations studied, in terms of age, tumour type and chemotherapy regimen, rhEPO use was associated with consistent benefits in terms of reduced transfusion requirements and improved haematological parameters. Only one case of darbepoietin use was reported.

Conclusions: While more studies are required, it appears that rhEPO is safe in this vulnerable patient group and can benefit children with cancer by preventing or ameliorating anaemia.     

Cost of adverse drug events related to potentially inappropriate medication use: A systematic review

BackgroundThe use of potentially inappropriate medications (PIMs) for older people is associated with worse health outcomes owing to the occurrence of adverse drug events (ADEs) and drug interactions, leading to increased health care costs.ObjectivesIdentify the costs of ADEs related to PIMs use, in addition to the costs predictors.MethodsA systematic review was conducted in the PubMed and Scopus databases (until February, 2022), and the report of this study was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Interventional and observational studies that reported costs of ADEs regardless of perspective (i.e., payer) were considered. Reporting and methodological quality were assessed using the tool proposed by Larg and Moss for evaluating cost-of-illness studies.ResultsA total of 20 (21 publications), published between 2001 and 2020, were included (236,888,744 older people). The ADEs costs related to PIMs use were mostly related to the use of health services (hospitalization [n = 7], health care expenses [n = 7], and emergency department visits [n = 3]). Among the 8 studies that reported P value, 7 identified higher costs for PIM users than non-PIM users. Three studies reported cost predictors, being highest number of PIMs in use, age older than 75 years, male gender, general health status in older people in use of benzodiazepines, and drug interactions in older people diagnosed as having dementia. Regarding to assessment of reporting and methodological quality, all studies had at least one limitation (answer “no”).ConclusionsOur findings suggest that PIMs use is associated with higher costs of hospitalization, health care expenses, and visits to emergency department owing to ADEs, regardless of PIMs in use, health service, perspective, and screening tools used for PIMs identification. However, these findings should be interpreted with caution because all studies had at least one methodological limitation.     

医疗机构药师干预促进合理用药管理的系统评价

目的:了解药师为规范临床药物治疗行为进行技术合作和技术干预的内容,以及我国开展合理用药工作的现状,为合理用药管理提供决策依据。方法:以干预、药学、药事和药师等检索词建立检索策略,通过文献计量学方法,统计、分析2005-2013年中国医院数字图书馆(CHKD)和万方医学网(Wanfang Med Online)发表的"药师参与合理用药工作管理"的相关文献;统计文献数量,分析汇总期刊分布。结果:检索2005-2013年发表的干预相关文献1 478篇,有效文献991篇,分布于196种杂志,相关论文在期刊中的分布并不均匀,具有明显的集中和离散规律;载文量前10位均为药学期刊,达404篇,载文量占40.77%,期刊占1.00%,显示较高的集中趋势。药师干预随年度逐步增长,干预内容随国家相关法规的颁布、政策的调整、管理工作的安排而变化。药事干预分层制策,因地制宜; 干预方法、形式及内容多样,干预对象涉及医、药、护及患者;根据工作内容,干预时机分事前、事中和事后干预;干预地点前移;干预适度;干预质量逐步提高。结论:我国医疗机构药师参与临床实践形式呈多样化,涵盖专科疾病治疗、抗凝门诊、处方管理、药物应用管理、治疗药物评价与分析、静脉输液配置、治疗药物监测、药物不良反应监测、药品临床应用数据分析、药物相关的健康教育及解决与药物有关的问题等专业性实践。临床实践证明,药师干预是规范药物相关医疗行为,促进药物合理使用的一种行之有效的手段之一;干预同时若叠加行政管理,建立规范的干预标准及干预质量评价体系,药师干预的效果会进一步提高。