剂量-反应Meta分析系列之非随机误差导致的偏倚的处理方法

作为一种有效的系统评价方法,剂量-反应Meta分析被广泛用于探讨自变量与因变量之间的因果关系,并且多基于观察性研究。观察性研究样本量大,进行Meta分析时可提供较为充分的统计效能。但由于自身设计问题,观察性研究容易混入多种偏倚,而这些偏倚可能会影响最终结果,导致其偏离真实值。因方法学上的盲区,当前并无特定针对剂量-反应Meta分析的偏倚校正方法,本文借鉴观察性研究Meta分析中的偏倚校正方法,通过调整后将其应用于剂量-反应Meta分析模型中,并对各类校正方法的优缺点进行归纳比较。     

湖北医药学院在校医学生循证医学知晓程度的横断面研究

目的了解湖北医药学院在校医学生对循证医学相关知识的知晓程度。方法采用预先设计的调查问卷分层随机抽取湖北医药学院600名不同专业、不同年级在校学生进行调查,调查时间为2013年5月10日-12日,采用Excel 2007软件进行统计分析。结果回收有效问卷545份,有效回收率为90.8%。58.5%的同学表示是首次听说"循证医学"这个术语或曾经听说过但毫无了解,38.2%的同学学习过,仅3.3%的同学对其比较熟悉;调查对象均建议学校开展循证医学教学。结论湖北医药学院在校医学生对循证医学的知晓程度整体较低,但学习态度积极,循证医学教学水平亟待提升。     

Advanced HER2-positive gastric cancer: Current and future targeted therapies

The prognostic value of human epidermal growth factor receptor 2 (HER2) in gastric cancer is controversial. Consensus guidelines have standardized the testing of HER2 status in gastric cancer. Overexpression of this receptor occurs in approximately 20% of gastric and gastro-esophageal junction adenocarcinomas, predominantly those of the intestinal type. Recently, trastuzumab has emerged as the first targeted drug to improve overall survival when combined with chemotherapy in advanced HER2-positive gastric cancer. Primary and secondary resistance to trastuzumab has become a major problem and new strategies to overcome this resistance are needed. A high percentage of advanced HER2-positive gastric cancer patients who progress on trastuzumab therapy are candidates for second-line therapy. New families of targeted drugs, including tyrosine kinase inhibitors (TKIs) such as lapatinib and PF-00299804, mammalian target of rapamycin (mTOR) pathway inhibitors such as everolimus, heat-shock protein 90 (HSP90) inhibitors such as AUY922, HER dimerization inhibitors such as pertuzumab, and antibody-chemotherapy conjugates such as trastuzumab-emtansine (T-DM1), could offer alternative second-line treatments when trastuzumab-based first-line therapy fails.     

Exploring the drug-induced anemia signals in children using electronic medical records

ABSTRACT

Objectives: The objectives were to identify drugs related with anemia in children and evaluate the novelty of these correlations.

Methods: The authors established a two-step method for detecting the relationship between drugs and anemia using electronic medical records (EMRs), which were obtained from 247,136 patients in Beijing Children’s Hospital between 2007 and 2017. The authors extracted potential drugs by mining cases for hemoglobin abnormalities from the EMR and then performed a retrospective cohort study to correlate them with anemia by calculating the matched odds ratios and 95% confidence interval using unconditional logistic regression analysis.

Results: In total, nine positive drug-anemia associations were identified. Among them, the correlations of drugs fluconazole (OR 3.95; 95%CI: 2.65–5.87) and cefathiamidine (OR 3.49; 95%CI: 2.94–4.15) with anemia were considered new signals in both children and adults. Three associations of drugs, vancomycin, cefoperazone-sulbactam and ibuprofen, with anemia were considered new signals in children.

Conclusion: The authors detected nine signals of drug-induced anemia, including two new signals in children and adults and three new signals in children. This study could serve as a model for using EMR and automatic mining to monitor adverse drug reaction signals in the pediatric population.     

Hyperalgesia in Opioid-Managed Chronic Pain and Opioid-Dependent Patients

This observational study aimed to determine whether pain sensitivity in patients with noncancer chronic pain, taking either methadone or morphine, is similar to patients maintained on methadone for dependence therapy, compared with a control group. Nociceptive thresholds were measured on a single occasion with von Frey hairs, electrical stimulation, and cold pressor tests. In all subjects receiving methadone or morphine, nociceptive testing occurred just before a scheduled dose. Cold pressor tolerance values in patients with noncancer, chronic pain, treated with morphine and methadone, were 18.1 ± 2.6 seconds (mean ± SEM) and 19.7 ± 2.3 seconds, respectively; in methadone-maintained subjects it was 18.9 ± 1.9 seconds, with all values being significantly (P < .05) lower than opioid-naïve subjects (30.7 ± 3.9 seconds). These results indicate that patients with chronic pain managed with opioids and methadone-maintained subjects are hyperalgesic when assessed by the cold pressor test but not by the electrical stimulation test. None of the groups exhibited allodynia as measured using the von Frey hairs. These results add to the growing body of evidence that chronic opioid exposure increases sensitivity to some types of pain. They also demonstrate that in humans, this hyperalgesia is not associated with allodynia.PerspectiveThis article presents an observational study whereby the pain sensitivity of patients with chronic pain managed with opioids and opioid-maintained patients were compared with opioid-naïve patients. The results suggest that opioid use may contribute to an increase in the sensitivity to certain pain experimental stimuli.     

The association between calcium supplement and preeclampsia and gestational hypertension: a systematic review and meta-analysis of randomized trials

Objectives: The purpose of this study is to investigate whether calcium supplement with or without other drugs could reduce the risk of preeclampsia and gestational hypertension based on existed evidence, and to clarify whether there is discrepant effect among different population and using different dose.

Methods: PubMed, Cochrane library, and EMBASE database were searched. Two authors independently screened all records and extracted data. The meta-analysis was performed to calculate risk ratios and 95% CIs using random-effects models.

Results: 27 studies, with 28 492 pregnant women were included. The results showed calcium supplement was associated with lower incidence of preeclampsia (RR 0.51, 95% CI: 0.40 to 0.64) and gestational hypertension (RR 0.70, 95% CI: 0.60 to 0.82). Sub-analyses revealed high-dose (1.2–2 g/day), moderate-dose (0.6–1.2 g/day), and low-dose (<0.6 g/day) of calcium supplement could reduce the risk of preeclampsia. For gestational hypertension, only high dose and moderate dose groups were associated with reducing the risk of gestational hypertension. However, we could draw a conclusion which does group was the most protective, as we were unable to directly compare the effects of different doses.

Conclusions: This study indicated calcium supplementation might decrease the risk of preeclampsia and gestational hypertension. And results of subgroups analyses enhanced our confidence to the protective effect of calcium supplementation. However, further studies with direct comparison of different dose of calcium supplementation are needed to explore the ideal dose of calcium supplementation to prevent preeclampsia and gestational hypertension.     

Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis

Context  Concern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear. Objective  To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials. Data Sources  MEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies. Study Selection  All English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes. Data Extraction  Trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes. Data Synthesis  From 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, –1.13; 95% confidence interval [CI], –1.70 to –0.57), 4 trials of clonidine (–0.95; 95% CI, –1.44 to –0.47), and 2 trials of gabapentin (–2.05; 95% CI, –2.80 to –1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined. Conclusion  The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.      

Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials

Context  Specific features of trial quality may be associated with exaggeration or shrinking of the observed treatment effect in randomized studies. Therefore, assessment of trial quality is often used in meta-analysis. However, the degree to which specific quality measures are associated with treatment effects has not been well established across a broad range of clinical areas. Objective  To determine if quality measures are associated with treatment effect size in randomized controlled trials (RCTs). Design  Quality measures from published quality assessment scales were evaluated in RCTs included in meta-analyses from 4 medical areas (cardiovascular disease, infectious disease, pediatrics, and surgery). Included meta-analyses incorporated at least 6 RCTs, examined dichotomous outcomes, and demonstrated significant between-study heterogeneity in the odds ratio (OR) scale. Main Outcome Measures  Relative ORs comparing overall treatment effect (summary OR) of high vs low-quality studies, as determined by each quality measure, with relative ORs less than 1 indicating larger treatment effect in low-quality studies. Results  Twenty-four quality measures were analyzed for 276 RCTs from 26 meta-analyses. Relative ORs of high vs low-quality studies for these quality measures ranged from 0.83 to 1.26; none was statistically significantly associated with treatment effect. The proportion of studies fulfilling specific quality measures varied widely in the 4 medical areas. In analyses limited to specific medical areas, placebo control, multicenter studies, study country, caregiver blinding, and statistical methods were significantly associated with treatment effect on 7 occasions. These relative ORs ranged from 0.40 to 1.74. However, the directions of these associations were not consistent. Conclusions  Individual quality measures are not reliably associated with the strength of treatment effect across studies and medical areas. Although use of specific quality measures may be appropriate in specific well-defined areas in which there is pertinent evidence, findings of associations with treatment effect cannot be generalized to all clinical areas or meta-analyses.      

Endocrine tumours and their significance to anaesthesia

Hormonally active tumours of the endocrine system are uncommon conditions, but they present a considerable anaesthetic challenge. The relative rarity of these tumours has meant that there are few, if any, comparative, controlled trials of one anaesthetic technique against another. Most of the management regimes advocated are based on anecdotal experience, and even though such experience may be considerable, it is difficult to establish one form of anaesthetic management as superior to another. This paper will review currently recommended approaches to the management of secreting endocrine tumours.