Tramadol and the occurrence of seizures: a systematic review and meta-analysis

Abstract

Introduction: Tramadol is a synthetic opioid which is commonly used around the world to relieve moderate to severe pain. One of the serious possible complications of its use is seizures. The present study aims to investigate and summarize the studies related to tramadol and occurrences of seizures after tramadol use and factors influencing these seizures.

Methodology: Our systematic review is compliant with PRISMA guidelines. Two researchers systematically searched PubMed/Medline, Web of Sciences, and Scopus. Cohort, case-control, cross-sectional studies, and clinical trials. The risk of bias was assessed using the Newcastle–Ottawa Scale After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed with using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn.

Results: A total of 51 articles with total sample size of 101 770 patients were included. The results showed that seizure event rate in the subgroups of tramadol poisoning, therapeutic dosage of tramadol, and tramadol abusers was 38% (95% CI: 27–49%), 3% (95% CI: 2–3%), 37% (95% CI: 12–62%), respectively. Tramadol dose was significantly higher in the patients with seizures than those without (mean differences: 0.82, CI 95%: 0.17–1.46). The odds for occurrence of seizures were significantly associated with male gender (pooled OR: 2.24, CI 95%: 1.80–2.77). Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15–1.49).

Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration. Given that, most of the evidence derives from studies utilizing a cross-sectional design, the association of tramadol with seizures should not be considered to be definitively established     

Prenatal exposure to misoprostol and congenital anomalies: systematic review and meta-analysis

The present systematic review was proposed with the objective of estimating the risk of congenital anomalies and other adverse events in children exposed to misoprostol during fetal life. The data source consisted of case–control studies that analyzed the effect of prenatal exposure to misoprostol on the pregnancy outcome, which were located in electronic databases and published up to June 2005. The outcomes of interest included congenital anomalies, fetal death, low birth weight and prematurity. The odds ratios (OR) for the individual studies were pooled by meta-analysis. Sensitivity tests and heterogeneity analysis were performed. Four studies involving 4899 cases of congenital anomalies and 5742 controls were included in accordance with the selection criteria. None of the studies analyzed other adverse effects from misoprostol on the outcome from gestation. Increased risks of congenital anomalies related to misoprostol use were found for any congenital defect (OR = 3.56; 95% CI: 0.98–12.98), Möbius sequence (OR = 25.31; 95% CI: 11.11–57.66) and terminal transverse limb defects (OR = 11.86; 95% CI: 4.86–28.90). In conclusion, prenatal exposure to misoprostol is associated with an increased risk of Möbius sequence and terminal transverse limb defects.     

Measles immunity in children: the 1985 national immunisation survey

In April 1985 a national immunisation survey was conducted, in the course of which blood samples were collected from approximately 3000 randomly selected children throughout the country. The study sample comprised approximately 1000 new school entrants, 1000 standard three pupils, and 1000 form four students. The sera were tested for morbilli antibody using an ELISA technique. Twenty-one percent of the five year olds lacked antibody, suggesting that an overall immunisation rate of about 80% is being achieved. Fourteen percent of the 15 year olds lacked antibody, suggesting that this rate of immunisation is partially interfering with the circulation of the wild virus. We conclude that a sizeable pool of susceptible adolescents is accumulating at a time when some wild virus activity still persists, and anticipate a shift in the peak age of measles infection from the 5-9 to the 10-15 age group. This unfortunate side effect of the national immunisation programme could be minimised by improving immunisation uptake in young childhood. Suggestions are made as to how this could be achieved.     

Exposure to fluconazole and risk of congenital malformations in the offspring: A systematic review and meta-analysis

Vulvovaginal candidiasis (VVC) affects up to 75% of women at least once during their lifetime, mostly during the reproductive age, and recurrence rate is about 50%. Because half of all pregnancies are unplanned and pregnant women have an increased risk of VVC recurrence, the likelihood of inadvertently being exposed to fluconazole in pregnancy is increased. Thus, we aimed to examine the risk of congenital malformations in the offspring of women exposed to fluconazole in the first trimester of pregnancy. The rate for overall malformations was 1.10 (95% CI 0.98–1.25), for heart defect was 1.29 (95% CI 1.05–1.58), for craniofacial defects was 1.25 (95% CI 0.88–1.77), and for limb/musculoskeletal defects was 0.82 (95% CI 0.59–1.13). In conclusion, the use of fluconazole in the first trimester does not appear to increase the overall risk for congennital malformations. More studies are needed to address the potential increased rate of heart defects.     

Hepatitis B in New Zealand children: the 1985 national immunisation survey

In April 1985 a national immunisation survey was conducted, in the course of which blood samples were collected from 3000 randomly selected children throughout the country. There were 1000 new school entrants (mean age 5 years), 1000 standard 3 pupils (mean age 10 years), and 1000 form 4 students (mean age 15 years). The sera were tested for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen, by ELISA. The prevalence of infection rose with age until by 15 years of age 13.1% of the study population (8.2% of the European and 42.0% of the Maori children) were marker positive. At all ages, Maori children were five times more likely to be positive for any marker, and approximately thirteen times more likely to be positive for antigen (actively infected), than the European children. Even when the data had been standardised for age and race, children resident in the eastern North Island were still almost three times more at risk than children in the South Island. Children in the remaining areas of the North Island were at approximately equal degrees of risk, intermediate between the high and low endemic areas mentioned. We conclude that universal childhood immunisation is necessary to control horizontal transmission of heptatis B virus in New Zealand.     

奥司他韦致神经精神不良事件国内外文献系统回顾性分析

目的 系统分析奥司他韦致精神异常的临床特点,为临床实践提供证据和建议。方法 计算机检索PubMed、Embase、中国生物医学文献数据库、中国知网、维普数据库和万方数据库,时间截止到2021年1月,纳入奥司他韦致神经精神不良事件的中英文病例报道,对文献进行筛选、数据归纳及统计。结果 最终纳入中英文文献19篇,22例患者（男10例,女12例）。中位年龄17岁,其中50%为18岁以下儿童。多数患者无基础疾病,68.2%的患者为联合用药,所有患者均无精神相关疾病史。不良反应表现为失眠、情绪异常、行为异常、幻觉、谵妄,严重者可出现自杀现象。68.2%的患者在服药2 d内出现不良反应症状,时间最长在服药4 d后出现症状。主要的治疗措施是立即停药,7例不良反应严重者使用抗精神病药物（主要为苯二氮类）,多数患者在停药2 d内症状均有所改善或消失,其中3例患者不良反应改善时间超过10 d,中位累积药量450 mg,最大累积药量750 mg,最小累积药量60 mg。不良反应关联性评价为肯定1例,很可能18例,可能3例。结论 神经精神事件是奥司他韦少见的不良反应,多表现为情绪异常、行为异常、幻觉、谵妄等,一般在用药2 d内发生,临床医生和药师应当主动告知患者及家属,发现精神异常现象应立即停药,及时就医,避免导致严重后果。     

Encephalopathy after high-dose Ifosfamide: a retrospective cohort study and review of the literature

BACKGROUND: Encephalopathy occurs in 10-40% of patients treated with high-dose ifosfamide. Proposed risk factors for encephalopathy include hepatic or renal dysfunction, brain metastases, electrolyte imbalances and drug-drug interactions. OBJECTIVE: The purpose of this retrospective cohort study and literature review was to estimate the prevalence of encephalopathy, identify characteristics associated with encephalopathy and evaluate the effectiveness of methylthioninium chloride (methylene blue) in its prevention. STUDY DESIGN AND METHODS: A total of 19 patients received high-dose ifosfamide for soft tissue sarcoma during a 4-year period at our medical centre. Eight patients developed encephalopathy based on adverse drug event (ADE) reports submitted by a clinical pharmacist. These reports incorporate the Naranjo probability scale, which is used to assess the likelihood that a change in clinical status is the result of an ADE rather than the result of other factors, such as progression of disease. The demographics, concurrent medication therapy, co-existing illnesses and laboratory parameters were documented from the medical records. We also conducted a review of the literature by searching MEDLINE (1996-October 2007). MAIN OUTCOME AND RESULTS: A total of 19 patients received high-dose ifosfamide; eight patients experienced encephalopathy (group I, 42%) and 11 patients did not experience encephalopathy (group II, 58%). More women than men developed encephalopathy (group I, 87.5% vs group II, 27.3%). Serum albumin (group I, 3.1 +/- 0.3 vs group II, 3.6 +/- 0.3 g/dL), haemoglobin (10.5 +/- 1.5 vs 12.4 +/- 1.7 g/dL) and total bilirubin (0.5 +/- 0.2 vs 0.8 +/- 0.3 mg/dL) levels were substantially lower in patients with encephalopathy, whereas the ratio of actual bodyweight to the ideal bodyweight (1.4 +/- 0.3 vs 1.1 +/- 0.2) was substantially higher in these patients. Five (62.5%) patients received a subsequent cycle of high-dose ifosfamide; all of these patients received methylthioninium chloride to minimize the risk of encephalopathy. All of these patients developed encephalopathy. Other reports have found that hypoalbuminaemia is associated with encephalopathy and that methylthioninium chloride does not prevent ifosfamide-induced encephalopathy. CONCLUSIONS: In summary, female sex, low total bilirubin, albumin and haemoglobin levels, and obesity appear to be associated with ifosfamide-induced encephalopathy. Methylthioninium chloride did not appear to prevent encephalopathy with subsequent doses of high-dose ifosfamide.     

霉酚酸酯在肝移植术后免疫抑制治疗中有效性和安全性的系统评价

目的:系统评价霉酚酸酯(MMF)在肝移植术后免疫抑制治疗中的有效性和安全性。方法:检索Pubmed、Embase、Medline、The Cochrane library、CNKI、VIP以及万方数据库,检索时间均从建库至2013年11月,纳入肝移植术后使用MMF进行免疫抑制治疗的随机对照试验(RCT)。在评价纳入研究的方法学质量和提取有效数据后,采用RevMan 5.0进行Meta分析。结果:共纳入11篇RCT,包括1 284例患者。Meta分析结果显示,在疗效指标方面,试验组与对照组在患者生存率、移植物存活率方面的差异无统计学意义,肾功能指标(血清肌酐、肾小球滤过率)试验组优于对照组,差异有统计学意义;在安全性指标方面,试验组胃肠道不适发生率大于对照组,差异有统计学意义;高血压发生率小于对照组,差异有统计学意义;2组在导致感染、高血糖方面的差异无统计学意义。结论:基于当前临床证据,MMF在肝移植术后免疫抑制治疗中的远期结果有待进一步研究。安全性方面,临床医生可根据具体情况,如患者是否有胃肠道疾病、高血压、高血糖等,选用相应药物。     

Publication misconduct and plagiarism retractions: a systematic,retrospective study

Abstract

Objectives:

To investigate whether plagiarism is more prevalent in publications retracted from the medical literature when first authors are affiliated with lower-income countries versus higher-income countries. Secondary objectives included investigating other factors associated with plagiarism (e.g., national language of the first author’s country affiliation, publication type, journal ranking).     

Reporting quality in systematic reviews of in vitro studies: a systematic review

Background: Systematic reviews (SRs) and/or meta-analyses of in vitro research have an important role in establishing the foundation for clinical studies. In this study, we aimed to evaluate the reporting quality of SRs of in vitro studies using the PRISMA checklist.

Method: Four databases were searched including PubMed, Virtual Health Library (VHL), Web of Science (ISI) and Scopus. The search was limited from 2006 to 2016 to include all SRs and/or meta-analyses (MAs) of pure in vitro studies. The evaluation of reporting quality was done using the PRISMA checklist.

Results: Out of 7702 search results, 65 SRs were included and evaluated with the PRISMA checklist. Overall, the mean overall quality score of reported items of the PRISMA checklist was 68%. We have noticed an increasing pattern in the numbers of published SRs of in vitro studies over the last 10 years. In contrast, the reporting quality was not significantly improved over the same period (p?=?.363). There was a positive but not significant correlation between the overall quality score and the journal impact factor of the included studies.

Conclusions: The adherence of SRs of in vitro studies to the PRISMA guidelines was poor. Therefore, we believe that using reporting guidelines and journals paying attention to this fact will improve the quality of SRs of in vitro studies.