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Medicine Correspondence Blog

The Medicine Correspondence Blog allows authors to post Letters to the Editors, Reviews, and other editorial writings that are not considered original research.

Wednesday, March 27, 2019

Dear professors:

We have carefully considered your comments. Please see our explanation below:

First, another study has reported that plasma exchange (PE) can not only remove poison but also has the ability to remove inflammatory mediators and other pathogenic factors1. Additionally, PE may have a wider utility such as for treating patients who deteriorate despite intensive care and those with toxicities or a worsening of central nervous system functionality1. The patient in our study had severe toxic encephalopathy that meets the above indications for PE, and it can be assumed that PE may help clear the inflammatory and pathogenic factors, which are induced by thallium poisoning. Furthermore, as reported2, thallium ion specifically binds with sulfur to form a macromolecule and may disrupt sulfhydryl dependent functions, most of which are pivotal for life. This forming of macromolecules with thallium ion is thought to play an important role in its pathogenesis, therefore, removal of these macromolecules, a potential pathogen, is believed to have a good effect on the clinical course. PE can get rid of some macromolecules, including those formed by sulfur-containing protein.

Second, we agree with your calculation, but evaluating the efficacy of PE is not just about the amount of thallium ions in the replacement fluid. As one study has report, the most important factor determining the clinical utility of PE is its ability to increase the total clearance of a toxin1. Take the first PE as an example, the blood thallium concentration was 280 ng/ml before PE and 250 ng/ml after PE; thus, the clearance rate (280-250)/280 was 10.7%, indicating that it had the ability to help remove thallium ions from the body. Our study also emphasizes that PE was combined with Prussian blue, and hence, the exact efficacy of PE still needs further verification. Furthermore, it is important to note that after treatment the patient's condition gradually improved, further indicating that our treatment is feasible. 

We are willing to invite professors to visit the patient with us to further understand the patient's condition. Finally, we again thank for your attention.


Author Correspondence 

Guodong Lin, Poisoning Treatment Department, Affiliated Hospital Academy of Military Medical Sciences

Zewu Qiu,  Affiliated Hospital of Academy of Military Medical Sciences, China

Email: qiuzw828@163.com

Yongan Wang, State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, China

Email: yonganw@126.com


References

[1] Schutt RC, Ronco C, Rosner MH. The role of therapeutic plasma exchange in poisonings and intoxications. Seminars in dialysis. Mar-Apr 2012;25(2):201-206.

[2] Tian YR, Sun LL, Wang W, et al. A case of acute thallotoxicosis successfully treated with double-filtration plasmapheresis. Clinical neuropharmacology. Nov-Dec 2005;28(6):292-294.


Wednesday, March 27, 2019

Dear Editors and Reviewers:

Sorry for delayed response. We are busy with other research recently, and have not noted the email. We appreciated that our article could have your attention. Here are detailed point-by-point responses to your comments are listed as follows:

1. I read with interest a recent article on systematic review and meta-analysis regarding the efficacy of pigtail catheters for pneumothorax by Fang et al. (1), and found several mistakes in the study. The authors stated that "the meta-analysis was based on 16 articles with a total of 1067 patients" in the abstract and showed "16 included articles" in Figure 1. However, there were "17 included studies" in the results and in Table 1, and the authors stated that "In this systematic review and meta-analysis of 1124 cases of pneumothorax from 18 articles…".

Response: Thanks. This meta-analysis included 16 articles with 17 studies, because referrence No.13 included 2 studies based on barotrauma and iatrogenic pneumothorax. But we are sorry for typos of the sentence "In this systematic review and meta-analysis of 1124 cases of pneumothorax from 18 articles…", it should be rephrased as following:" In this systematic review and meta-analysis of 1067 cases of pneumothorax from 16 articles…".

2. Moreover, two of the articles (references No. 19 and 21 of the article) listed in Table 1 included patients with pleural effusion (2) and with pleural effusion, empyema, and anterior mediastinal collection (3) in addition to those with pneumothorax. These mistakes are obvious and question the validity of the meta-analysis.

Response: Thanks. We have noted this during the analysis. However, considering the integrity of the included data, only patients with pneumothorax in two of the articles (references No. 19 and 21 of the article) were enrolled in this meta-analysis. In this study, we performed sensitive analysis and Egger'test for publication bias, and they showed reliable results. In addition, we assessed the effect of causes of pneumothorax (spontaneous, secondary, traumatic, and iatrogenic) and patient characteristics (children and adults) in order to explore the possible origin of heterogeneity. Thus we thought this meta-analysis may be reliable.


Author Correspondence

Dr. Ming Fang

Email: fangminghi@163.com


Thursday, March 7, 2019

We read with interest the recent paper by Lin and colleagues (1) and while we commend them on their care of a critically ill patient, we have concerns regarding the interpretation of their plasma exchange data.  While many of the critical parameters needed to evaluate the efficacy of plasma exchange (PE), such as patient weight, are omitted or not explicitly stated in the report,(2) enough data are available to provide an approximation. Using a “best-case” estimate of the volume of distribution of thallium at 3L/kg and an assumed patient weight of 50kg we can deduce the following:

Blood [thallium] at the first PE (on figure 1) = 280ng/mL = 280mcg/L

Total body content of thallium at the time of the 1st PE: 50kg x 3L/kg x 280mcg/L = 42,000 mcg = 42mg

[Thallium] in effluent at the 1st PE (on figure 1) = 120ng/mL = 120mcg/L

Effluent volume during the 1st PE (as stated in the supplemental material) = 1.95L

Amount of thallium removed by the 1st PE = 1.95L x 120mcg/L = 234mcg = 0.234mg

Percentage of thallium removed during 1st exchange = 0.234mg/42mg = 0.55%

According to EXTRIP’s criteria for “dialyzability”, these results are considered “non-dialyzable”.(3) Given these data, we conclude that plasma exchange was inconsequential. The interpretation of a decreasing blood thallium concentration as evidence of the efficacy of plasma exchange is misleading due to the large volume of distribution of thallium, and the cumulative effects of endogenous clearance and to prussian blue. As noted by the authors the benefit of plasma exchange is most evident for toxins that are highly protein bound and thallium has no protein binding.(4) While we agree that the precise role of intermittent hemodialysis and hemoperfusion is not entirely determined in patients with thallium poisoning (5) we argue that this report speaks strongly against the use of plasma exchange. Intermittent hemodialysis in this case might have removed more thallium, at lower cost, and risk to the patient.


Author Correspondence

Robert S. Hoffman, MD, Division of Medical Toxicology, NYU School of Medicine, USA

Marc Ghannoum, MD FRCP, Department of Medicine University of Montreal, Verdun Hospital, Canada

Sophie Gosselin, MD FRCP, Emergency Department Hôpital Charles-Lemoyne, Canada


References

[1] Lin G, Yuan L, Bai L, Liu Y, Wang Y, Qiu Z. Successful treatment of a patient with severe thallium poisoning in a coma using Prussian blue and plasma exchange: A case report. Medicine (Baltimore). 2019;98(8):e14629.  

[2] Lavergne V, Ouellet G, Bouchard J, et al. Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology. Semin Dial. 2014;27(4):407-414.  

[3] Lavergne V, Nolin TD, Hoffman RS, et al. The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology. Clin Toxicol (Phila). 2012;50(5):403-413.

[4] Ghannoum M, Hoffman RS, Gosselin S, Nolin TD, Lavergne V, Roberts DM. Use of
extracorporeal treatments in the management of poisonings. Kidney Int. 2018;94(4):682-688. 

[5] Ghannoum M, Nolin TD, Goldfarb DS, et al. Extracorporeal Treatments in Poisoning Workgroup. Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2012;7(10):1682-1690.


Tuesday, February 12, 2019

I was greatly interested in the systematic review and meta-analysis by Lanaro et al. suggesting osteopathic manipulative treatment is clinically effective in reducing the length of stay (LOS) and costs in a large population of preterm infants.[1] Within this review my attention was drawn to Lanaro et al. use of a fixed effect model for calculating their primary outcome: length of hospital stay (LOS). They included five studies (n= 1306, 645 preterm were allocated in the OMT group and 661 to the control group) in their meta-analysis. The application of a fixed effect model depends on two assumptions that should be met: 1. One believes that all the studies included in the analysis are functionally equivalent and 2. that one has the goal to compute a common effect size for the identified population, and not to generalize to other populations.[2] An example for such a case would be a pharmaceutical company that uses thousand patients to compare a drug versus a placebo. The company might run a series of trials which can be considered identical in the sense that it is reasonable to assume that any variables that have an impact on the outcome should be the same across them. Further, we assume that the patients, the treatment dose, the outcomes measures and the timepoints are essentially the same. In that instance since all the studies share a common effect and the first condition is met. It also meets the second goal because the goal of the analysis which is to see if the drug works in the population from which the patients were drawn.[3]

In the case of the meta-analysis of Lanaro et al. the use of a fixed effect model is inappropriate for the meta-analysis. The study population arises form different clinics and from two different countries. The studies used different treatment techniques, different treatment durations and different frequencies of treatment. Control group conditions also differed across the trials. These reasons make it unlikely that a fixed effect model is the right choice for the analysis. A further indication of the heterogeneity between included studies is found in the relatively high I² value of I²=61%[4], which can be considered moderate to high.[5]

A more appropriate model for the meta-analysis of the studies is a random effects meta-analysis because it does not assume a common effect size.[6] Recreating the analysis (using RevMan Version 5.2.6) with a random effects model the overall effect is no longer statistically significant (p = 0.08) [see figure 1]. This significantly alters the conclusion that osteopathic manipulative treatment does reduce LOS and costs in preterm infants.

Authors should choose models whose assumptions best fit the research question and those assumptions should be considered in the interpretation of the data.

I would like to thank Dr Neil OConnell for his comments on this letter.


Author Correspondence

Tobias Saueressig, Dipl.-Volkswirt, PT

Email: t.saueressig@gmx.de

Tel: 0049-202-27249596

Website: https://physiomeetsscience.com


References

[1] Lanaro, Diego, et al. "Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis." Medicine 96.12 (2017).

[2] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

[3] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

[4] Lanaro, Diego, et al. "Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis." Medicine 96.12 (2017).

[5] Higgins, Julian PT, et al. "Measuring inconsistency in meta-analyses." BMJ: British Medical Journal 327.7414 (2003): 557.

[6] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

Monday, February 4, 2019

​I read with interest a recent article on systematic review and meta-analysis regarding the efficacy of pigtail catheters for pneumothorax by Fang et al. (1), and found several mistakes in the study. The authors stated that "the meta-analysis was based on 16 articles with a total of 1067 patients" in the abstract and showed "16 included articles" in Figure 1. However, there were "17 included studies" in the results and in Table 1, and the authors stated that "In this systematic review and meta-analysis of 1124 cases of pneumothorax from 18 articles…". Moreover, two of the articles (references No. 19 and 21 of the article) listed in Table 1 included patients with pleural effusion (2) and with pleural effusion, empyema, and anterior mediastinal collection (3) in addition to those with pneumothorax. These mistakes are obvious and question the validity of the meta-analysis.


Author Correspondence

Hui-Ling Huang, NP, Department of Intensive Care Medicine, Chi Mei Medical Center, Taiwan

Email: ling890765@gmail.com

Telephone: +886-6-2812811 ext 57106


References

[1] Fang M, Liu G, Luo G, Wu T. Does pigtail catheters relieve pneumothorax?: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2018 Nov;97(47):e13255. doi: 10.1097/MD.0000000000013255.

[2] Cantin L, Chartrand-Lefebvre C, Lepanto L, et al. Chest tube drainage under radiological guidance for pleural effusion and pneumothorax in a tertiary care university teaching hospital: review of 51 cases. Can Respir J 2005;12:29–33.

[3] Gammie JS, Banks MC, Fuhrman CR, et al. The pigtail catheter for pleural drainage: a less invasive alternative to tube thoracostomy. JSLS 1999;3:57–61.

The authors of this article provided a response which can be found at this link